ArticleLiterature Review

Non-celiac Gluten Sensitivity

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Abstract

Gluten sensitivity has been best recognized and understood in the context of two conditions, celiac disease and wheat allergy. However, some individuals complain of symptoms in response to ingestion of "gluten," without histologic or serologic evidence of celiac disease or wheat allergy. The term non-celiac gluten sensitivity (NCGS) has been suggested for this condition, although a role for gluten proteins as the sole trigger of the associated symptoms remains to be established. This article reviews the available information regarding symptomatology, epidemiology and genetics, serology and histology, and in vitro and in vivo experimental data on the pathophysiology of NCGS.

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... 1 International consensus statements have defined non-celiac gluten sensitivity (NCGS) as a condition in which ingestion of gluten induces gastrointestinal and extra-intestinal symptoms in the absence of celiac disease or wheat allergy. 2,3 The condition represents a diagnostic problem because there are no reliable biomarkers and the clinical picture overlaps with irritable bowel syndrome (IBS). 2 A standardized double-blind placebo-controlled food challenge (DBPCFC) has been proposed as a diagnostic tool to confirm NCGS. 4 However, the clinical value of DBPCFC is questionable. 2,5,6 The pathogenesis of NCGS is not completely understood. ...
... 2,3 The condition represents a diagnostic problem because there are no reliable biomarkers and the clinical picture overlaps with irritable bowel syndrome (IBS). 2 A standardized double-blind placebo-controlled food challenge (DBPCFC) has been proposed as a diagnostic tool to confirm NCGS. 4 However, the clinical value of DBPCFC is questionable. 2,5,6 The pathogenesis of NCGS is not completely understood. Negative serology for specific antibodies and lack of association with HLA DQ2/DQ8 suggest a limited involvement of adaptive immune mechanisms. ...
... 21 GSRS-IBS is a selfadministered 13-items questionnaire, with a 7-point Likert scale for each item ranging from 1 ¼ 'no symptoms' to 7 ¼ 'severe symptoms,' and with an overall score range of 13-91. There are 5 GSRS sub-dimensions with their respective score ranges: pain (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), bloating (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21), constipation (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), diarrhea , and satiety (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The secondary outcome was daily gastrointestinal symptoms prospectively measured by a 100-mm visual analogue scale (VAS) for pain, bloating, passage of wind, nausea, stool dissatisfaction, and overall gastrointestinal symptoms. ...
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Background & aims: Non-celiac gluten sensitivity is characterized by symptom improvement after gluten withdrawal in absence of celiac disease. The mechanisms of non-celiac gluten sensitivity are unclear, and there are no biomarkers for this disorder. Foods with gluten often contain fructans, a type of fermentable oligo-, di-, monosaccharides and polyols. We aimed to investigate the effect of gluten and fructans separately in individuals with self-reported gluten sensitivity. Methods: We performed a double-blind crossover challenge of 59 individuals on a self-instituted gluten-free diet, for whom celiac disease had been excluded. The study was performed at Oslo University Hospital in Norway from October 2014 through May 2016. Participants were randomly assigned to groups placed on diets containing gluten (5.7 g), fructans (2.1 g), or placebo, concealed in muesli bars, for 7 days. Following a minimum 7-day washout period (until the symptoms induced by the previous challenge were resolved), participants crossed over into a different group, until they completed all 3 challenges (gluten, fructan, and placebo). Symptoms were measured by gastrointestinal symptom rating scale irritable bowel syndrome (GSRS-IBS) version. A linear mixed model for analysis was used. Results: Overall GSRS-IBS scores differed significantly during gluten, fructan, and placebo challenges; mean values were 33.1±13.3, 38.6±12.3, and 34.3±13.9, respectively (P = .04). Mean scores for GSRS bloating were 9.3±3.5, 11.6±3.5, and 10.1±3.7, respectively, during the gluten, fructan, and placebo challenges (P = .004). The overall GSRS-IBS score for participants consuming fructans was significantly higher than for participants consuming gluten (P = .049), as was the GSRS bloating score (P = .003). Thirteen participants had the highest overall GSRS-IBS score after consuming gluten, 24 had the highest score after consuming fructan, and 22 had the highest score after consuming placebo. There was no difference in GSRS-IBS scores between gluten and placebo groups. Conclusions: In a randomized, double-blind, placebo-controlled crossover study of individuals with self-reported non-celiac gluten sensitivity, we found fructans to induce symptoms, measured by the gastrointestinal symptom rating scale irritable bowel syndrome version.Clinicaltrials.gov no: NCT02464150.
... Os recursos disponíveis no tratamento da afecção incluem planos medicamentosos ou cirúrgicos que apresentam como foco a infertilidade e a dor pélvica crônica os quais são tidos como sintomas usuais da endometriose. 13 16,17,18,19 Já a SNCG é uma situação clínica associada à presença de sintomas intestinais e extraintestinais que ocorrem em consequência à ingestão de alimentos que contém glúten e que cessam quando há remoção deste mesmo componente da dieta, tendo sido previamente investigada e excluída as condições de DC e AG, isto é, quando a sorologia Brazilian Journal of Development, Curitiba, v.7, n.5, p. 53254-53268 may. 2021 apresenta-se negativa para a presença de anticorpos transglutaminase tecidual (antiTG) e anti-endomísio (EMA), é descartada a deficiência de IgA e a histopatologia duodenal obtida é normal. ...
... 2021 apresenta-se negativa para a presença de anticorpos transglutaminase tecidual (antiTG) e anti-endomísio (EMA), é descartada a deficiência de IgA e a histopatologia duodenal obtida é normal. 16,17,18 O anticorpo antigliadina (AGA) pode ser identificado em alguns pacientes, demonstrando a presença de biomarcador de reação imunológica ao glúten positiva. 16 As questões que abordaram a presença de diarreia e/ou fezes moles não apresentaram alterações nas médias dos questionários pré e pós-dieta. ...
... 16,17,18 O anticorpo antigliadina (AGA) pode ser identificado em alguns pacientes, demonstrando a presença de biomarcador de reação imunológica ao glúten positiva. 16 As questões que abordaram a presença de diarreia e/ou fezes moles não apresentaram alterações nas médias dos questionários pré e pós-dieta. ...
Article
Overview and Aims: Identify patients with surgically confirmed endometriosis and with gastrointestinal symptomatology by assessing whether there is clinical improvement of these from the adoption of gluten-free diet (GFD). Study design: They were invited to participate in the study by the researchers through telephone calls and instant messaging applications after selection in the clinics of attending physicians. Population: Through the GSRS (Gastrointestinal Symptom Rating Scale) questionnaire, the relationship of GFD adherence to symptomatology attenuation and benefit in the quality of life of 48 patients was analyzed. Methods: Inclusion criteria: female patients with surgical confirmation of endometriosis who agreed to participate in the study in accordance with the Informed Consent Form (ICF). Exclusion criteria: patients who already performed GFD, patients diagnosed with celiac disease, gluten allergy or non-celiac sensitivity to gluten, presence of gastrointestinal comorbidities, severe diseases or cognitive alterations that prevented the study from being performed. The patients who obtained the top 20 scores were invited to adopt GFD for one month, among those selected, only 12 proposed to participate in the diet. However, three of these presented personal complications that prevented the continuation of the same. After this period, a new questionnaire was applied to measure the impact of the diet on quality of life. Results: Nine patients finished the proposed period for the diet, with the average score obtained in the pre-diet questionnaire reducing from 57.2 to 36 in the post-diet. Conclusion: There was an improvement in gastrointestinal complaints of most patients and consequently in quality of life with GFD.
... While CeD affects one percent of the general population, the epidemiology of NCGS is still evolving [25][26][27]. Some studies suggest that the prevalence of NCGS in the general population may be up to 5% although other studies suggest lower prevalence [18,[28][29][30]. The reason why some patients develop CeD and others NCGS is not well known. ...
... The reason why some patients develop CeD and others NCGS is not well known. While up to 90% of patients with CeD have specific genetic susceptibility represented by genes of the major histocompatibility complex (HLA-DQ2 and -DQ8 haplotype, HLA: Human leukocyte antigen), these genes show up in NCGS patients at a much lower level of 50%, but a level of 30% is characteristic of the general population [14,18,29,30]. Furthermore while both adaptive and innate immune responses are involved in CeD, in NCGS, innate immune response to gluten peptides may be the predominant immune reaction [17,18,22,31,32]. ...
... Furthermore, it is possible that the gut microbiota play a role in driving the immune process in certain individuals towards CeD (if they have specific genetic susceptibility factors) while driving other individuals to NCGS. By producing gluten-degrading enzymes, oral and intestinal microbiota might convert an immunogenic gluten-peptide to non-immunogenic peptide thus leading to a cascade of events directed towards NCGS [17,18,22,[29][30][31][32]. ...
Article
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The spectrum of gluten-related disorders has widened in recent times and includes celiac disease, non-celiac gluten sensitivity, and wheat allergy. The complex of symptoms associated with these diseases, such as diarrhea, constipation or abdominal pain may overlap for the gluten related diseases, and furthermore they can be similar to those caused by various other intestinal diseases, such as irritable bowel syndrome (IBS). The mechanisms underlying symptom generation are diverse for all these diseases. Some patients with celiac disease may remain asymptomatic or have only mild gastrointestinal symptoms and thus may qualify for the diagnosis of IBS in the general clinical practice. Similarly, the overlap of symptoms between IBS and non-celiac gluten sensitivity (NCGS) often creates a dilemma for clinicians. While the treatment of NCGS is exclusion of gluten from the diet, some, but not all, of the patients with IBS also improve on a gluten-free diet. Both IBS and NCGS are common in the general population and both can coexist with each other independently without necessarily sharing a common pathophysiological basis. Although the pathogenesis of NCGS is not well understood, it is likely to be heterogeneous with possible contributing factors such as low-grade intestinal inflammation, increased intestinal barrier function and changes in the intestinal microbiota. Innate immunity may also play a pivotal role. One possible inducer of innate immune response has recently been reported to be amylase-trypsin inhibitor, a protein present in wheat endosperm and the source of flour, along with the gluten proteins.
... 'psychiatric') patients belonging to a sort of 'no man's land' of gluten related disorders [4]. Nonetheless, with the increasing number of patients complaining of symptoms following gluten ingestion, the awareness of a new gluten-related syndrome (currently referred to as non-celiac gluten sensitivity, NCGS) grows with a progressive pace over the years [5][6][7][8][9]. ...
... The increasing number of patients who experience symptoms after gluten ingestion without evidence of CD and WA has contributed to the recognition of NCGS as a new gluten-related disorder [5,7,16]. Although the existence of NCGS has been accepted worldwide, the knowledge regarding this syndrome is still limited, with many aspects awaiting further definition [6]. ...
Article
Non allergy-non-celiac wheat sensitivity (NCWS) has become a common and often overrated diagnosis. Skepticism mainly relates to patients with prominent intestinal symptoms in the absence of general or intestinal signs of inflammation. There is consensus that the major wheat sensitivities, celiac disease and wheat allergy, have to be ruled out which may be difficult for wheat allergy. The non-inflammatory intolerances to carbohydrates, mainly lactose and FODMAPs (fermentable oligi-, di-, monosaccharides and polyols), which cause bloating or diarrhoea, can usually be excluded clinically or by simple tests. Recent studies and experimental data strongly indicate that NCWS exists in a substantial proportion of the population, that it is an innate immune reaction to wheat and that patients often present with extraintestinal symptoms, such as worsening of an underlying inflammatory disease in clear association with wheat consumption. Wheat amylase-trypsin inhibitors (ATIs) have been identified as the most likely triggers of NCWS. They are highly protease resistant and activate the toll-like receptor 4 (TLR4) complex in monocytes, macrophages and dendritic cells of the intestinal mucosa. Non-gluten containing cereals or staples display no or little TLR4 stimulating activity. Wheat ATIs are a family of up to 17 similar proteins of molecular weights around 15 kD and represent 2-4% of the wheat protein. With oral ingestion they costimulate antigen presenting cells and promote T cell activation in celiac disease, but also in other immune-mediated diseases within and outside the GI tract. Copyright © 2015. Published by Elsevier Ltd.
... There is no clear evidence that only gluten can cause a clinical picture characteristic of NCGS. More research is needed on the subject [34]. ...
... Nie ma jednoznacznego dowodu na to, że tylko gluten może wywołać obraz kliniczny charakterystyczny dla NCGS. Potrzebne jest więcej badań na ten temat [34]. ...
Article
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More and more evidence confirms the theory that the intake of cereal products containing gluten may play an important role in the pathogenesis of many diseases. There are also premises indicating the relationship between the so-called gluten-related diseases and the development and course of mental disorders, including schizophrenia. The aim of this article is to review the literature on the potential relationship between the consumption of gluten and schizophrenia, considering the etiopathogenesis and the role of gluten-free diet in the treatment of schizophrenia. Methods: There were analysed available research papers in PubMed and Google Scholar with the key words: schizophrenia, gluten- related disorders, allergy to grain products, celiac disease, microbiota, immune system, exorphins and time span: 1960-2016 . Conclusions: Existing research results indicate a possible relationship between diet rich in grain products with high gluten content and the occurrence or exacerbation of schizophrenia symptoms. However, further studies are necessary to: 1) identify groups of patients for whom the consumption of cereal products (gluten) is associated with a particular risk of schizophrenia exacerbation, 2) determine the mechanisms relating the consumption of gluten with the mental state of schizophrenic patients, 3) get the possible benefits of implementing gluten-free diet in patients with schizophrenia.
... There is no clear evidence that only gluten can cause a clinical picture characteristic of NCGS. More research is needed on the subject [34]. ...
... Nie ma jednoznacznego dowodu na to, że tylko gluten może wywołać obraz kliniczny charakterystyczny dla NCGS. Potrzebne jest więcej badań na ten temat [34]. ...
Article
Full-text available
In this article the adverse effects of laparoscopic CO2 pneumoperitoneum and coelomic climate change, and their potential prevention by warmed, humidified carbon dioxide insufflation are reviewed. The use of pressurized cold, dry carbon dioxide (C02) pneumoperitoneum causes a number of local effects on the peritoneal mesothelium, as well as systemic effects. These can be observed at a macroscopic, microscopic, cellular and metabolic level. Local effects include evaporative cooling, oxidative stress, desiccation of mesothelium, disruption of mesothelial cell junctions and glycocalyx, diminished scavenging of reactive oxygen species, decreased peritoneal blood flow, peritoneal acidosis, peritoneal hypoxia or necrosis, exposure of the basal lamina and extracellular matrix, lymphocyte infiltration, and generation of peritoneal cytokines such as IL-1, IL-6, IL-8 and TNFα. Such damage is increased by high CO2 insufflation pressures and gas velocities and prolonged laparoscopic procedures. The resulting disruption of the glycocalyx, mesothelial cell barrier and exposure of the extracellular matrix creates a cascade of immunological and pro-inflammatory events and favours tumour cell implantation. Systemic effects include cardiopulmonary and respiratory changes, hypothermia and acidosis. Such coelomic climate change can be prevented by the use of lower insufflation pressures and preconditioned warm humidified CO2. By achieving a more physiological temperature, pressure and humidity, the coelomic microenvironment can be better preserved during pneumoperitoneum. This has the potential clinical benefits of maintaining isothermia and perfusion, reducing postoperative pain, preventing adhesions and inhibiting cancer cell implantation in laparoscopic surgery.
... Evidence is fairly strong for a generous intake of dietary fiber over the life span (156), with whole grains representing an important source. Advocacy for the inclusion of whole grains in the diet is widespread (153), but concerns about the contributions of grains to obesity have been expressed quite vocally (34), in particular concerns about the rising prevalence of gluten sensitivity (108) and concerns about genetic modifications of wheat (158). ...
... Clinical trial data are available and generally support efforts to reduce the glycemic load of the diet. Studies focused on this strategy have demonstrated benefits in the areas of weight loss, insulin metabolism, diabetes control, inflammation, and vascular function (108). Benefits have been seen in studies of both adults and children (118). ...
Article
Full-text available
Homelessness is a devastating experience for children and their families. Families, the majority of whose members are children, now comprise more than one-third of the overall homeless population. Most of these children are less than six years old. Various assumptions have driven policy and the allocation of resources to programs serving these families. Although decades of research and field experience suggest strategies for preventing and reducing this problem, perspectives differ, hindering the development of effective solutions. In this article, we explore some of these assumptions, including ( a) definitions of homelessness used to count the numbers of families and determine resource allocation, ( b) the needs of children and responses to the impact of adverse childhood experiences, and ( c) whether services matter and should be integrated with affordable housing. We conclude by suggesting various directions to ensure that these children are protected and have the opportunity to grow and thrive. Expected final online publication date for the Annual Review of Public Health, Volume 41 is April 1, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
... Over the last few years, there has been a resurgence in research interest regarding NCGS, as demonstrated by several scientific contributions on this topic. [15][16][17][18] Nevertheless, our knowledge is still limited, and there are many unresolved points warranting clarification. On the one hand, NCGS is a symptom-based condition, in which diagnosis remains highly presumptive, being exclusively based on clinical criteria and on exclusion of celiac disease and wheat allergy. ...
Article
Full-text available
Background and objectives: Buckwheat (Fagopyrum esculentum) is a gluten-free grain with acclaimed benefi-cial effects on human health. Our aim was to assess the effect of buckwheat products on intestinal/extra-intestinal symptoms and biochemical parameters in patients with Non-Celiac Gluten Sensitivity (NCGS). Methods and study design: A randomized, crossover trial with two intervention phases was conducted on 19 NCGS patients over a 12 week-period. The participants were assigned to consume products made from buckwheat or to maintain their normal gluten-free diet for 6 weeks in a random order. Symptoms due to NCGS were evaluated using two questionnaires. Results: During the intervention period with buckwheat products, patients experienced a signifi-cant decrease in the severity of abdominal pain and bloating (p=0.03). In contrast, the control group showed a significant worsening trend for the majority of NCGS symptoms such as nausea, headache, joint/muscle pain, and attention disorders. The replacement diet with buckwheat products also resulted in a significant increase of serum magnesium (+4.7%) and a significant reduction in the circulating levels of some pro-inflammatory cytokines such as interferon gamma (-33.3%) and monocyte chemotactic protein-1 (-46.5%). Conclusion: The study supports the positive effects of buckwheat for NCGS patients, showing that this alternative cereal can contribute to the re-duction of both negative gastro-intestinal and related symptoms, and nutritional deficiencies, and lead to an im-provement in inflammatory profile.
... Algorithms have been proposed for diagnosis of the spectrum of gluten-related disorders (Figure 1). 8,21 Diagnosis of celiac disease is primarily carried out through serologic testing for antigliadin, antiendomysium, and antitransglutaminase antibodies. These serologic tests are coupled with a small-bowel biopsy for histopathological assessment of the gut, the gold standard for diagnosing celiac disease. ...
... associated with gliadin intake in children include growth inhibition, absorbtional disorder, chronic diahorrea and abdominal distension.[5,6]In adults it causes fatigue, diahorrea and weight loss due to malabsorption.[7]Most importantly, this protein is also reported to bring in severe intestinal damage.[8]Literature survey confirms the presence of excess repeats of proline and glutamine residues in them.[9,10]Their ...
... A double-blind, placebo-controlled (DBPC) challenge has been suggested to confirm NCGS diagnosis [104]. It is possible to use an open food challenge, but there is a higher probability of false positive results because of important placebo effects [105]. ...
Article
In the last decade, the ingestion of gluten, a heterogeneous complex of proteins present in wheat, rice, barley and probably in oats, has been associated with clinical disorders, such as celiac disease, wheat allergy and recently to non-celiac gluten sensitivity or wheat intolerance syndrome. Gluten-related disorders, which are becoming epidemiologically relevant with an estimated global prevalence of about 5%, require the exclusion of gluten from the diet. For the past 5 years, an important shift in the availability of gluten-free products, together with increased consumption in the general population, has been recorded and is estimated to be about 12–25%. Many people follow a self-prescribed gluten-free diet, despite the fact that the majority have not first been previously excluded, or confirmed, as having gluten disorders. They rely on claims that a gluten-free diet improves general health. In this review, we provide an overview of the clinical disorders related to gluten or wheat ingestion, pointing out the current certainties, open questions, possible answers and several doubts in the management of these conditions. • KEY MESSAGE • Incidence of gluten-related disorders is increased in the last decade and self-diagnosis is frequent with inappropriate starting of a gluten-free diet. • Gluten and wheat are considered as the most important triggers to coeliac disease, wheat allergy and non-celiac gluten sensitivity. • Pediatricians, allergologist and gastroenterologist are involved in the management of these conditions and appropriate diagnostic protocols are required.
... Whenever being in suspicion of having celiac disease, a detailed medical history (especially pertaining to diet), physical examination, serology, upper endoscopy and histopathological analysis of multiple biopsies of the duodenum should be pursued to confirm the diagnosis [4] . Care should be taken not to confuse celiac disease with other forms of gluten sensitivity conditions in which the patient complains from symptoms similar to those of celiac disease but without showing the serologic or histological features of the latter [5] . These conditions have been termed non-celiac gluten sensitivity (NCGS). ...
Article
Background and objectives: Celiac disease is a disease affecting the digestive system whereby the patient is unable to tolerate gluten-containing food. The aims of this study were to study the prevalence of dental defects and oral hygiene status of a group of celiac disease patients in Benghazi. Materials and methods: A group of celiac disease patients (n = 40 & Male: Female ratio is 1: 2.4 & age range 3-19 years, mean 10 years, SD ± 4.8) were recruited from Benghazi Pediatric Hospital where they had already been diagnosed in gastroenterology units at private clinics. The patient’s dental status was assessed through measuring their Decayed, Missing and Filled Teeth index (DMFT), oral hygiene index (OHI) and CPITN using disposable mouth mirrors, explorers and periodontal probes. Descriptive statistics was applied to give a picture about the oral hard and soft tissue prevalence this group of patients. Results: Descriptive statistics of the celiac sample showed that 29 (72.5%) had enamel hypoplastic defects. The mean and SD values for DMFT, CPITN and OHI were measured (DMFT: 4.5 SD ± 4.7 & CPITN: 0.8 SD ± 0.5; and OHI: 1.1 SD ± 0.7). Besides, only two patients (6.4%) reported a history of oral ulceration during the course of their therapy. Healthy controls showed comparative values, being less in only OHI, while they were slightly more in DMFT and CPITN. Conclusion: This is a cross-sectional clinical survey showing that patients with celiac disorder should be expected to have higher prevalence of defective incisor teeth, which makes their front teeth liable to traumatic fracture. The presence of frequent soft tissue ulcers in their mouths might indicate a warning sign of the possibility to develop the disease and thus urge the child’s parents or guardians to consult a physician to confirm or negate the suspicion.
... A new syndrome of gluten intolerance, non coeliac gluten sensitivity (NCGS), has been described. NCGS can be diagnosed in those patients with gluten intolerance who do not develop antibodies that are typical neither of CD nor of wheat allergy and who do not suffer from lesions in the duodenal mucosa [43]. Although disease characteristics of NCGS are overlapping with irritable bowel syndrome (IBS), a recent study observed that an associated autoimmune disease was present in 14 % of patients with NCGS, which was mainly autoimmune thyroiditis and sporadically T1DM [44]. ...
Article
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This review aims at summarizing the present knowledge on the clinical consequences of concomitant coeliac disease (CD) in adult patients with type 1 diabetes mellitus (T1DM). The cause of the increased prevalence of CD in T1DM patients is a combination of genetic and environmental factors. Current screening guidelines for CD in adult T1DM patients are not uniform. Based on the current evidence of effects of CD on bone mineral density, diabetic complications, quality of life, morbidity and mortality in patients with T1DM, we advise periodic screening for CD in adult T1DM patients to prevent delay in CD diagnosis and subsequent CD and/or T1DM related complications.
... However, considering the excellent sensitivity and specificity of anti-TG2 and (and to a lesser extent anti-deamidated gliadin) antibodies, as well as the high negative predictive value of HLA-DQ2/DQ8 markers for celiac disease, it can be concluded with high certainty that the overwhelming majority of autism patients with elevated antibody to gliadin do not have celiac disease. If future studies prove the existence of sensitivity to gluten in a subset of patients with autism, the gluten-associated symptoms in such individuals may fall within the spectrum of ''non-celiac gluten sensitivity'' [28]. ...
... 47 Although the symptoms of NCGS are similar to those of celiac disease, however, unlike the celiac disease, the NCGS does not have a genetic predisposition, the role played by the immune system is not clear, it is not associated with malabsorption and vitamin or nutrient deficiency and is not linked to a higher risk of autoimmune diseases or intestinal neoplasias. 17 As it is not possible to differentiate celiac disease by a NCGS by symptoms alone or with the disappear- ance of these with a gluten-free diet [48][49][50] and there are currently no specific diagnostic tests, therefore remains a diagnosis of exclusion after the diagnostic tests for celiac disease or wheat allergy were negative. Recently, the Salerno Experts' Criteria 47 want to help the clinician to reach a firm diagnosis and positive NCGS. ...
Article
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Celiac disease (CD) is a complex polygenic disorder, which involves genetic factors human leukocyte complex (HLA) and non-HLA genes, environmental factors, innate and adoptive immunity, and a robust chronic T-mediated autoimmune component. The main goal of the present monograph is to define a methodological approach for the disease, characterized by frequent late diagnosis, in order for the physician to become aware of the disease management, the diversity of the clinical presentation itself and in different patients. A unique attention is payed to the specific diagnostic tests to define a correct and accurate application of them, and in addition, to disease follow-up and possible complications. Moreover, a dedicated space is assigned to refractory CD, to potential CD and non-celiac gluten sensitivity. Legislative aspects of the celiac disease in Italy are addressed, too. The celiac disease guidelines and their evaluation by means of Appraisal of Guidelines, Research and Evaluation II instrument allow us to classify the different recommendations and to apply them according to the stakeholders’ involvement, pertinence, methodological accuracy, clarity and publishing independence. Finally, the most current scientific evidence is taken into account to create a complete updated monograph.
... Ludvigsson et al., 95 in their study of about 28 Swedish provenbiopsy CD registers, evidenced a weak association between autism and CD but they found a strong association between autism, positive CD serology and histologically normal intestinal mucosa. GFD is becoming more popular in autistic communities 92 and these gluten-associated symptoms may be considered into the spectrum of "non-celiac gluten sensitivity", 96 but are needed larger studies about this topic. ...
Article
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Celiac disease (CD) determines neurologic manifestations in 10% of all CD patients. We describe the most common clinical manifestations as cerebellar ataxia, gluten encephalopathy, multiple sclerosis, peripheral neuropathies, sensorineural hearing loss, epilepsy, headache, depression, cognitive deficiencies and other less described clinical conditions. Our aim is to perform, as more as possible, a review about the most recent update on the topics in international literature. It is important to consider clinical neurological manifestations in celiac patients and to research these conditions also in the follow-up because they may start also one year after the start of gluten free diet (GFD) as peripheral neuropathy. The association with autism is analysed and possible new association with non-celiac gluten sensitivity (NCGS) are considered.
... The gluten-sensitive immune response is independent of the presence of antigens HLADQ2 / DQ8. In celiac disease, they play a key role in the presentation of immunogenic peptides included in the gluten specific T lymphocytes in the small intestine [55]. In celiac disease, the prevalence of HLADQ2 / DQ8 is 95%, while in case of sensitivity to gluten, their presence is confirmed in only about 50% of cases, which is a value slightly higher than in the general population (30%) [53]. ...
Article
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Despite over 100-year history of research on schizophrenia, its etiology is still not fully understood, which might be due to the significant heterogeneity in terms of both its course, as well as the etiopathogenesis. One of the best-proven mediating mechanisms in the development of schizophrenia is the immuno-inflammatory response, the sources of which are believed to be the dysfunctions of brain-gut axis and pathological processes occurring in the intestines. This paper is a review of the literature on this subject which presents factors both involved in the functioning of brain-gut axis and important for the development of schizophrenia, i.e. 1. intestinal microbiome (intestinal microbiota), 2. permeable intestine (leaky gut syndrome), 3. hypersensitivity to food antigens, including gluten and casein of cow's milk. Research results seem to be very promising and indicate the possibility of improved clinical outcomes in some patients with schizophrenia by modifying diet, use of probiotics, and the implementation of antibiotic therapy of specific treatment groups. However, further research is needed on links between the intestinal microbiome and intestinal function as factors mediating the activation of the immune system and the development and further course of schizophrenia.
... W nadwrażliwości na gluten odpowiedź immunologiczna jest niezależna od obecności antygenów HLADQ2/DQ8. W celiakii odgrywają one kluczową rolę przy prezentacji immunogennych peptydów wchodzących w skład glutenu, specyficznym limfocytom T w jelicie cienkim [55]. W celiakii rozpowszechnienie HLADQ2/DQ8 wynosi 95%, podczas gdy w nadwrażliwości na gluten ich obecność stwierdza się jedynie w około 50% przypadków, co stanowi wartość niewiele wyższą niż w populacji ogólnej (30%) [53]. ...
Article
Full-text available
Despite over 100-year history of research on schizophrenia, its etiology is still not fully understood, which might be due to the significant heterogeneity in terms of both its course, as well as the etiopathogenesis. One of the best-proven mediating mechanisms in the development of schizophrenia is the immuno-inflammatory response, the sources of which are believed to be the dysfunctions of brain-gut axis and pathological processes occurring in the intestines. This paper is a review of the literature on this subject which presents factors both involved in the functioning of brain-gut axis and important for the development of schizophrenia, i.e. 1. intestinal microbiome (intestinal microbiota), 2. permeable intestine (leaky gut syndrome), 3. hypersensitivity to food antigens, including gluten and casein of cow’s milk. Research results seem to be very promising and indicate the possibility of improved clinical outcomes in some patients with schizophrenia by modifying diet, use of probiotics, and the implementation of antibiotic therapy of specific treatment groups. However, further research is needed on links between the intestinal microbiome and intestinal function as factors mediating the activation of the immune system and the development and further course of schizophrenia.
... Algorithms have been proposed for diagnosis of the spectrum of gluten-related disorders (see Figure 1). 13,19 Diagnostic criteria for celiac disease and wheat allergy have been established. ...
Article
Full-text available
Gluten-free diets have gained popularity with the public at a rate greater than would be expected based on the prevalence of gluten-related disorders such celiac disease, nonceliac gluten sensitivity, and wheat allergy. This article reviews gluten-related disorders, indications for gluten-free diets, and the possible health benefits of gluten. Despite the health claims for gluten-free eating, no published experimental evidence supports weight-loss with a gluten-free diet or suggests that the general population would benefit from avoiding gluten.
... This approach is quite a complicated procedure in practice, given the difficulty in preparing the intervention products, the need for highly trained personnel and high costs. 118 An alternative is the open food challenge, but this might render false-positive results. 119 Confirming the diagnosis of NCGS is important to avoid unnecessary dietary restrictions and the possibility of missing coeliac disease. ...
Article
Gluten-related disorders such as coeliac disease, wheat allergy and noncoeliac gluten sensitivity are increasingly being diagnosed in children. Coeliac disease occurs frequently, affecting 1-3% of the Western population. The condition manifests at a very young age, more so in girls, and is related to the HLA genotype. Coeliac disease might be considered a public health problem and, as primary prevention is not possible, the debate on mass screening should be reopened. Wheat proteins, including gluten, are responsible for one of the most common food allergies in children: wheat allergy. Unlike coeliac disease and wheat allergy, noncoeliac gluten sensitivity is an unclear and controversial entity. These three gluten-related disorders are treated with a gluten-free diet. In coeliac disease, the diet should be strictly followed, whereas wheat allergy only requires wheat elimination and in noncoeliac gluten sensitivity occasional trials of gluten reintroduction can be done. A good diagnostic work-up is important for gluten-related disorders in childhood to avoid unnecessary restrictive diets in children. In this Review, we provide an overview of the pathogenesis, diagnosis and management of the most common gluten-related disorders in children.
... Therefore, the main role of HLA-DQ typing in the diagnosis of CD is to exclude the disease [6,10,11]. In particular, application of HLA-DQ2 and -DQ8 typing is recommended to exclude CD in patients with equivocal small bowel biopsy (SBB) finding or those following a Gluten-free diet [7,12,13] and patients with non-celiac gluten sensitivity [1,14,15]. HLA-DQ2 and -DQ8 typing is also recommended for CD screening in high-risk individuals including first-degree relatives of a confirmed case and patients with autoimmune and non-autoimmune conditions known to be associated with CD, such as type 1 diabetes mellitus, Down syndrome, and Turner syndrome [7,16]. ...
Article
Full-text available
Purpose: Celiac disease (CD) diagnosis can be established by serological and small bowel biopsy (SBB), while absence of HLA-DQ2 and -DQ8 haplotypes excludes the disease. The present study aims at evaluating the diagnosis of a representative sample of pediatric and adult CD patients of Gaza strip in light of DQ2 and DQ8 haplotypes expression. Methods: Unrelated CD patients (n = 101) and matched healthy controls (n = 97) were genotyped for DQA1*05, DQB1*02 and DQB1*03:02 alleles by allele-specific real-time PCR. The diagnosis was re-evaluated according to the patient laboratory tests and HLA-DQ genotype. Results: The diagnosis of 35 patients who have been managed for CD could not be confirmed. Twenty-five of them were diagnosed upon their clinical presentation only. The remaining were either negative for serological and SBB tests or negative for HLA-DQ haplotypes. The HLA-DQ alleles were negative in 4 SBB and one Anti-EMA positive patients. The frequency of DQ2 and DQ8 haplotypes among the remaining 65 confirmed cases was 70.8 and 15.4%, respectively, compared to 17.5 and 27.8% in the controls. The DQB1*02 allele was the most common in the cases (84.6%) followed by DQA1*05 allele (80%) and DQB1*03:02 allele (20%). The DQA1*05 allele was commonest in the control group (54.6%) followed by DQB1*02 allele (42.3%) and DQB1*03:02 allele (28.9%). Conclusions: Absence of HLA-DQ2 and HLA-DQ8 genotyping in the workup of patients may result in CD misdiagnosis, particularly in a setting with poor histopathological diagnostic capacity.
... To the best of our knowledge, there are no data suggesting that the condition follows the same HLA-DQ2/-DQ8 association as CD. However, some studies suggest that approximately 50% of patients with non-celiac gastroenteropathy have the HLA-DQ2/-DQ8 haplotype compared with 30% of the general population (20). There are no serological tests or histological features to diagnose NCGS, and the clinical workup for diagnosis of NCGS usually focuses initially on the exclusion of CD and wheat allergy. ...
Article
Aim: Herein, we present five children and adolescents with a final diagnosis of non-celiac gluten sensitivity (NCGS). Background: Non-celiac gluten sensitivity (NCGS) is a condition characterized by gastrointestinal and extra-intestinal symptoms triggered by ingestion of gluten-containing compounds, e.g., wheat, rye, and barley, in subjects without celiac disease or wheat allergy. Methods: Demographic characteristics, clinical manifestations, serum biomarkers and skin prick test were evaluated. Patient data was also recorded after they followed a gluten-free diet (GFD). Height and weight were measured, and all patients were examined 6 months after following the suggested GFD. Results: All patients had failure to thrive and abdominal pain. Clinical symptoms were reduced, and significant weight and height gains were detected after 1 month of following a gluten-free diet. Conclusion: The relationship between failure to thrive (FTT) and NCGS is still unknown; hence, NCGS may be one of the main causes of FTT which can be prevented by gluten-free diets.
... Nous proposons une adaptation aux soins primaires de l'algorithme proposé dans la littérature anglosaxonne [90], en cas de présentation du patient avec des symptômes évocateurs de SII (voir figure ci-après). ...
Thesis
Le syndrome de l'intestin irritable (SII) est un trouble digestif fonctionnel trèsfréquemment rencontré en médecine générale. Depuis quelques années, certains patients atteints de troubles digestifs fonctionnels ont expérimenté un amendement de leurs symptômes en excluant le gluten de leur alimentation. Dénommé sensibilité au gluten (SG), cette nouvelle entité parmi les troubles liés au gluten est définie par des réactions cliniques (digestives ou extradigestives) qui apparaissent à l'ingestion de gluten, et disparaissent à son exclusion, alors que la maladie coeliaque et l'allergie au blé ont été éliminées. Ce concept étant récent et pouvant remettre en cause la prise en charge du syndrome de l'intestin irritable, nous avons réalisé une revue de la littérature pour tester l'hypothèse selon laquelle l'ingestion de gluten peut être responsable d'un syndrome de l'intestinirritable.Les données de la littérature sont encore trop peu nombreuses. La méthodologie decertaines études est souvent critiquable, mais la plupart a analysé l?impact du gluten surl'histologie duodénale. Seules trois études à ce jour, dont 2 études randomisées ontutilisé la référence diagnostique des troubles liés au gluten, non allergiques et noncoeliaques : un régime sans gluten suivi d?une réintroduction du gluten en doubleaveugle contrôlée placebo. Cela permet effectivement de confirmer l'existence d'unesensibilité au gluten non coeliaque.2 observations cliniques de médecine générale, présentées en complément du travailbibliographique, indiquent une efficacité du régime sans gluten sur le score de qualitéde vie IBS-QOL.La découverte de cette nouvelle entité devrait avoir un impact concret dans la pratiquequotidienne du médecin généraliste lors de la prise en charge d'un SII. Outre le fait dediminuer la prescription de certains examens complémentaires inutiles et couteux, celapermettrait pour un sous groupe non négligeable de patients atteints de SII de découvrirune réponse tangible et durable à leurs problèmes digestifs chroniques
... As the impact of the continued ingestion of nutritionally unbalanced GF foods on the health of consumers is countless, contributing to the development of associated diseases, such as chronic constipation, type 1 diabetes, thyroid malfunction, anaemia, and overweight [55][56][57][58], these pastas are a breakthrough in terms of specially designed foods for this target population. Commercial GF cereal foods, made of refined flours or starches, are also of lower nutritional value compared to their wheat counterparts [59]. ...
Article
Full-text available
Seaweed is a novel source of important nutritional compounds with interesting biological activities that could be processed into added-value products, namely gluten-free foods. In this study, two previously developed products obtained from Laminaria ochroleuca processing (liquid extract and a purée-like mixture) were incorporated in gluten-free (GF) pasta in order to develop functional products especially designed for the celiac population. The raw and cooked pastas were characterized in terms of their cooking quality parameters, nutritional composition, texture and rheological properties, and antioxidant activity. It was found that the developed GF pastas had similar mechanical and texture characteristics to the control. Both supplemented GF pastas presented a significantly (p < 0.05) higher fibre and mineral content than the control pasta.
... Recent studies, including a placebo-controlled clinical trial have shown the existence of an entty known as non-celiac gluten-sensitvity. [44][45][46] This entty appears in patents who, having no duodenal histological lesion nor genetc predispositon to CD, have symptoms triggered by gluten consumpton. There are stll important problems in defning these patents since many authors consider that the defniton encompasses those who have positve celiac disease genetcs (40% of these patents are HLA-DQ2 positve) and lymphocytc duodenal infltraton. ...
... La sensibilité au gluten non coeliaque est peut-être une forme d'intolérance au gluten où les marqueurs de la maladie coeliaque (IgA antitransglutaminase) sont absents. Les IgG anti-gliadine peuvent être présents isolément, mais seulement chez 56 % à 65 % des patients ayant une sensibilité au gluten non coeliaque et 81 % des maladies coeliaques confirmées [49,113]. Il n'y a pas de trouble de la perméabilité intestinale, ni d'atrophie des villosités intestinales sur la biopsie duodénale, mais il y a souvent une infiltration lymphocytaire dans la sous-muqueuse. ...
Article
Full-text available
De plus en plus de personnes dans les pays développés attribuent à une intolérance alimentaire diverses manifestations cliniques de typestroubles gastro-intestinaux, douleurs articulaires voire polyarthrite rhumatoïde (PR), migraine ou fatigue chronique. Plusieurs auteurs ont rapportéune fréquence plus importante de la positivité des IgG anti-aliments chez les patients souffrant de syndrome de l’intestin irritable (SII), de maladiesinflammatoires chroniques de l’intestin (MICI) ou de PR comparés aux témoins sains. Depuis une décennie, ces dosages de recherche sontdisponibles en routine sur prescription médicale mais aussi en accès libre sans avis médical via internet. Ces dosages sont utilisés pour établir desrégimes d’éviction des aliments pour lesquels la recherche d’IgG est positive, dans l’espoir d’une amélioration des symptômes supposés être enrelation avec la consommation de ces aliments par le biais d’une réaction d’intolérance faisant intervenir les IgG. L’objectif de ce travail est derappeler les mécanismes impliqués dans les intolérances et allergies alimentaires, et le rôle physiologique des réponses immunitaires à IgG. Lestechniques de dosage des IgG anti-aliments commercialement disponibles sont passées en revue. Les principales études basées sur le dosage desIgG anti-aliments appliqué à diverses pathologies font l’objet d’une analyse critique, suivie d’une discussion. Il en ressort que l’intérêt clinique desdosages d’IgG anti-aliments est l’objet d’une vive polémique en raison de leur mauvaise valeur prédictive positive. Les recommandations établiessur la base de ces dosages sont susceptibles de faire prendre un risque au patient en retardant quelquefois le bon diagnostic ou en lui faisant suivreun régime alimentaire d’éviction le plus souvent inutile et parfois délétère pour sa santé. Les coûts directs liés aux dosages et indirects occasionnéspar les régimes d’éviction, souvent élevés, peuvent être évités au profit d’autres stratégies diagnostiques. En conclusion, dans l’état actuel des connaissances médicales, les dosages d’IgG anti-aliments ne devraient plus être pratiqués en routine pour établir un diagnostic d’intolérance ouallergie alimentaire à IgG, ni mettre en place un régime d’éviction. Leur utilisation devrait être réservée à des fins de recherche.
... La sensibilité au gluten non coeliaque est peut-être une forme d'intolérance au gluten où les marqueurs de la maladie coeliaque (IgA antitransglutaminase) sont absents. Les IgG anti-gliadine peuvent être présents isolément, mais seulement chez 56 % à 65 % des patients ayant une sensibilité au gluten non coeliaque et 81 % des maladies coeliaques confirmées [49,113]. Il n'y a pas de trouble de la perméabilité intestinale, ni d'atrophie des villosités intestinales sur la biopsie duodénale, mais il y a souvent une infiltration lymphocytaire dans la sous-muqueuse. ...
... La sensibilité au gluten non coeliaque est peut-être une forme d'intolérance au gluten où les marqueurs de la maladie coeliaque (IgA antitransglutaminase) sont absents. Les IgG anti-gliadine peuvent être présents isolément, mais seulement chez 56 % à 65 % des patients ayant une sensibilité au gluten non coeliaque et 81 % des maladies coeliaques confirmées [49,113]. Il n'y a pas de trouble de la perméabilité intestinale, ni d'atrophie des villosités intestinales sur la biopsie duodénale, mais il y a souvent une infiltration lymphocytaire dans la sous-muqueuse. ...
Article
There is an increasing tendency in western countries to attribute to food intolerance various clinical types of gastrointestinal disorders, joint pain or rheumatoid arthritis (RA), migraine and chronic fatigue. Several authors have reported a greater frequency of positive anti-food IgG in patients presenting irritable bowel syndrome (IBS), chronic inflammatory bowel disease (IBD) and RA compared to healthy controls. Over the last decade, screening tests have become routinely available on prescription but are also freely available over the Internet. These assays are used to create diets that avoid IgG-positive foods in the hope of improving symptoms thought to be related to the consumption of these foods associated with IgG-mediated intolerance reactions. The purpose of this study is to review the mechanisms involved in food intolerance and the physiological and pathological role of IgG immune response. Commercially available assays for food IgG are reviewed. Studies based on anti-food IgG determination applied to various diseases are reviewed and discussed. Considerable controversy surrounds the clinical relevance of anti-food IgG assays because of their poor positive predictive value. The recommendations made on the basis of these assays are likely to jeopardize the health of patients by delaying correct diagnosis or encouraging them to follow a mostly useless and occasionally harmful diet. The frequently high direct and indirect costs of assays and avoidance diets may be avoided in favor of other diagnostic strategies. Finally, in the current state of medical knowledge, anti-food IgG tests should not be performed routinely to establish a food intolerance diagnosis or to devise an avoidance diet. They should be used solely for research purposes.
... Wheat is the basis of human nutrition, yet the consumption of specific components of wheat, including gluten, amylase trypsin inhibitor, (ATI) and fermentable oligo-, di-, monosaccharide, (FODMAPs) can cause abdominal pain, bloating, vomiting, diarrhoea, constipation, headache, tiredness, urticarial, dermatitis, numbness, neuropsychiatric disorders malabsorption of nutrients and ataxia [1][2][3][4]. Most of these symptoms are common to different wheat/ gluten-related disorders including wheat allergy, celiac disease (CD) and the recently described non-celiac wheat sensitivity (NCWS) [3,[5][6][7][8]. CD, the best know gluten-related disorder, is an inflammatory disease induced by gluten ingestion in genetically susceptible individuals. ...
Article
Full-text available
Non-celiac wheat sensitivity (NCWS), also referred to as non-celiac gluten sensitivity, is a recently described disorder triggered by wheat/gluten ingestion. NCWS elicits a wide range of symptoms including diarrhoea, intestinal discomfort, and fatigue in analogy with other wheat/gluten-related disorders and celiac disease in particular. From the pathological standpoint, NCWS patients only have a slight increase of intraepithelial lymphocytes, while antibodies to tissue transglutaminase (tTG) and villous atrophy, otherwise diagnostic features of celiac disease, are absent. To date, the diagnosis of NCWS relies on symptoms and exclusion of confounding diseases, since biomarkers are not yet available. Here, the expression levels of selected miRNAs were examined in duodenal biopsies and peripheral blood leukocytes collected from newly diagnosed patients with NCWS and, as controls, from patients with celiac disease and gluten-independent gastrointestinal problems. We identified a few miRNAs whose expression is higher in the intestinal mucosa of patients affected by NCWS in comparison to control patients affect by gluten-independent dyspeptic symptoms (Helicobacter pylori-negative) and celiac disease. The present study provided the first evidence that NCWS patients have a characteristic miRNA expression patterns, such peculiarity could be exploited as a biomarker to the diagnosis of this disease.
... 10 Over the last 3 years the experts of gluten related disorders have started again to work on this condition as shown by the two Consensus Conferences, held in London (2011) and Munich (2012), and by several scientific original papers and reviews on this topic. 1,2,6,7,[11][12][13][14] Although there is a general agreement that NCGS does exist, our knowledge on this syndrome is still lacking with many aspects waiting to be clarified. Scarce information has been generated on its pathogenesis, epidemiology and diagnostic biomarkers. ...
Article
Full-text available
Non-celiac gluten sensitivity is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. Gluten is likely responsible for the clinical picture in a subset of patients, whereas in other cases it concurs to this syndrome together with fermentable mono-oligo-disaccharides and polyols and wheat proteins (e.g., amylase trypsin inhibitors). Innate immunity plays a pivotal role in the development of this syndrome, which is characterized by gut inflammation without villous atrophy and likely changes of intestinal barrier function. Data on its epidemiology are still undefined and largely variable. In the USA its prevalence varies from 0.6% to 6% in primary or tertiary care, respectively. Clinically, patients complain of gastrointestinal and extra-intestinal symptoms triggered by the ingestion of gluten without evidence of celiac disease and wheat allergy. Intestinal symptoms resemble those of irritable bowel syndrome, whereas neurological signs are quite common among extra-intestinal manifestations. So far, there are no biomarkers for non-celiac gluten sensitivity, but about half of patients shows anti-gliadin antibodies of immunoglobulin G class. Although not specific for non-celiac gluten sensitivity, the detection of such antibodies can support the diagnosis in patients with gluten-related symptoms. In the absence of diagnostic biomarkers a double-blind, placebo-controlled food challenge is currently the best way for confirming non-celiac gluten sensitivity. Studies aimed at clarifying the pathophysiological, clinical and laboratory features of non-celiac gluten sensitivity will help a better management of patients with this novel and intriguing clinical entity.
... A recent meta-analysis of several studies further validates the presence of significantly increased levels of antibody to gliadin among patients with non-hereditary ataxia [74]. There have been suggestions that gluten ataxia would fit better within the spectrum of non-celiac wheat/gluten sensitivity (NCWS) rather than celiac disease, based on serologic, histologic, and genetic markers [75,76]. In 2008, a novel neuronal transglutaminase, TG6, was reported as a target autoantigen in patients with gluten ataxia [77]. ...
Article
Full-text available
Increased antibody reactivity towards self-antigens is often indicative of a disruption of homeostatic immune pathways in the body. In celiac disease, an autoimmune enteropathy triggered by the ingestion of gluten from wheat and related cereals in genetically predisposed individuals, autoantibody reactivity to transglutaminase 2 is reflective of the pathogenic role of the enzyme in driving the associated inflammatory immune response. Autoantibody reactivity to transglutaminase 2 closely corresponds with the gluten intake and clinical presentation in affected patients, serving as a highly useful biomarker in the diagnosis of celiac disease. In addition to gastrointestinal symptoms, celiac disease is associated with a number of extraintestinal manifestations, including those affecting skin, bones, and the nervous system. Investigations of these manifestations in celiac disease have identified a number of associated immune abnormalities, including B cell reactivity towards various autoantigens, such as transglutaminase 3, transglutaminase 6, synapsin I, gangliosides, and collagen. Clinical relevance, pathogenic potential, mechanism of development, and diagnostic and prognostic value of the various identified autoantibody reactivities continue to be subjects of investigation and will be reviewed here.
... La sensibilité au gluten non coeliaque est peut-être une forme d'intolérance au gluten où les marqueurs de la maladie coeliaque (IgA antitransglutaminase) sont absents. Les IgG anti-gliadine peuvent être présents isolément, mais seulement chez 56 % à 65 % des patients ayant une sensibilité au gluten non coeliaque et 81 % des maladies coeliaques confirmées [49,113]. Il n'y a pas de trouble de la perméabilité intestinale, ni d'atrophie des villosités intestinales sur la biopsie duodénale, mais il y a souvent une infiltration lymphocytaire dans la sous-muqueuse. ...
... La sensibilité au gluten non coeliaque est peut-être une forme d'intolérance au gluten où les marqueurs de la maladie coeliaque (IgA antitransglutaminase) sont absents. Les IgG anti-gliadine peuvent être présents isolément, mais seulement chez 56 % à 65 % des patients ayant une sensibilité au gluten non coeliaque et 81 % des maladies coeliaques confirmées [49,113]. Il n'y a pas de trouble de la perméabilité intestinale, ni d'atrophie des villosités intestinales sur la biopsie duodénale, mais il y a souvent une infiltration lymphocytaire dans la sous-muqueuse. ...
Article
Full-text available
Introduction Les examens biologiques sont d’un apport important pour le diagnostic et le suivi des allergies ou la recherche de facteurs prédisposant à celles-ci. L’utilisation optimisée de ces outils nécessite une actualisation constante des connaissances. En France, le texte de recommandations de la Haute Autorité de santé (HAS) date de 2005. La mise à disposition des allergènes moléculaires et l’évolution des stratégies diagnostiques a rendu indispensable une actualisation de ces recommandations, qui a été initiée sous l’impulsion de la Société française d’allergologie. Méthodes Nous avons utilisé la méthode de Recommandation pour la pratique clinique (RPC) élaborée par la HAS pour rédiger des recommandations concises, gradées par niveaux de preuve, répondant aux questions posées. Ces recommandations ont été relues par un groupe de relecture incluant les professionnels et usagers concernés, puis validées par un groupe de validation. Les liens d’intérêt des rédacteurs ont été déclarés selon les exigences de la HAS. Résultats Nous avons identifié 63 questions, objet de ces recommandations de bonne pratique, dont 11 sur les allergies respiratoires, 28 sur les allergies alimentaires, 11 sur les allergies aux médicaments, 8 sur les allergies aux piqûres et morsures d’arthropodes et 5 sur d’autres pathologies allergiques. La majorité des recommandations relèvent d’un niveau de preuve de grade C. Un préambule aborde 16 questions d’ordre plus général, liées à la biologie de l’allergie. Discussion Ces recommandations n’ont pas vocation à décrire l’ensemble des outils pour le diagnostic ou le suivi des maladies allergiques, mais concernent des points d’amélioration de la prise en charge de l’allergie, identifiés à l’aide de recommandations consensuelles nationales et internationales ou d’études de pratiques publiées depuis 2005. En l’absence de telles données, l’avis et l’expérience du groupe de travail a été exprimé. Conclusion Ces recommandations de bonne pratique de prescription et d’interprétation des examens biologiques pour le diagnostic et le suivi des hypersensibilités allergiques selon la méthode RPC de la HAS, apportent en 2018 une actualisation rendue nécessaire par l’évolution des concepts et des outils.
Chapter
As an important component of wheat, rye, and barley, gluten can be found in a large variety of foods consumed throughout the world (breads, pasta, pizza, etc.). However, the introduction of gluten-containing grains in the human diet about 10,000 years ago created the conditions for human diseases related to gluten exposure. These reactions to gluten represent a heterogeneous set of conditions, including celiac disease, non-celiac gluten sensitivity, and wheat allergy, which combined affect about 10 % of the general population. These three conditions represent distinct pathophysiological reactions to gluten ingestion, with differing clinical presentations, serological markers, and long-term treatments. Though current research strives to clarify the boundaries between these entities, their differences can be difficult to distinguish. This chapter provides an overview of the ever-evolving definitions of gluten-related disorders.
Chapter
Non-celiac gluten/wheat sensitivity (NCWS) is characterized by a range of intestinal and extraintestinal symptoms in response to ingestion of wheat and related cereals in individuals in whom celiac disease and wheat allergy are ruled out. Recent data support the existence of a biological basis for NCWS, as demonstrated by several dietary intervention trials and the discovery of biomarkers of immune activation and compromised intestinal barrier in patients. Despite the fact that the condition is more commonly known as a gluten sensitivity, the identity of the molecular component(s) of wheat responsible for triggering the associated symptoms remains a subject of debate and research. Gluten proteins, amylase/protease inhibitor proteins, and fermentable carbohydrates are among the various possible culprits proposed based on preclinical or clinical data. This review is aimed at examining the evidence, including the strength of the available data and their potential relevance to the pathogenic mechanism and clinical presentation of NCWS.
Article
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Non-celiac gluten or wheat sensitivity (NCWS) is a “clinical entity induced by the ingestion of wheat leading to intestinal and/or extraintestinal symptoms that improve once the wheat-containing foodstuff is removed from the diet, and celiac disease and wheat allergy have been excluded”. This mostly accepted definition raises several points that remain controversial on this condition. In the present review, the authors summarize the most recent advances in the clinic and research on NCWS through an accurate analysis of different studies. We screened PubMed, Medline, Embase, and Scopus using the keywords “non-celiac gluten sensitivity”, “non-celiac wheat sensitivity”, and “diagnosis”. We would like to emphasize two main points, including (A) the controversial clinical and etiological aspects in different trials and experiences with particular attention to the Salerno criteria for the diagnosis of NCWS and (B) the histological aspects. The etiology of NCWS remains controversial, and the relationship with irritable bowel syndrome is obscure. Histologically, the duodenal mucosa may show a variable pattern from unremarkable to a slight increase in the number of T lymphocytes in the superficial epithelium of villi. The endorsement of this disease is based on a positive response to a gluten-free diet for a limited period, followed by the reappearance of symptoms after gluten challenge. The Salerno expert criteria may help to diagnose NCWS accurately. Social media and inaccurate interpretation of websites may jeopardize the diagnostic process if individuals self-label as gluten intolerant.
Article
Background and aims: Non-Celiac Gluten Sensitivity (NCGS) is a recently proposed clinical condition causing both intestinal and extra-intestinal symptoms, without gastrointestinal lesions, which improve on avoiding gluten intake, in the absence of celiac disease and wheat allergy. The prevalence of this condition is still a matter of debate, in part due to the very recent introduction of an accepted diagnostic test, a double-blind, placebo controlled gluten challenge. However, this is a lengthy and cumbersome procedure, theoretically burdened by a significant reduction of patient compliance. ALCAT 5 is an automated in vitro test evaluating the toxic effect of gluten on neutrophils by the exposure of these cells to a gluten-containing extract of gluten-containing cereals. The test is very simple to perform, the results are rapidly obtained, and might represent, if sufficiently accurate, a promising alternative to diagnose gluten intolerance. The aim of this study was the comparison of ALCAT 5 results with those of a double-blind, placebo-controlled, gluten challenge, in a group of patients with clinically-suspected NCGS. Methods: Twenty-five patients (M/F 3/22, mean age 32 ± 4 yrs) with severe functional abdominal pain and bloating, who had previously undergone the ALCAT 5 test, were enrolled. All the subjects reported their symptoms on a gluten-containing diet and considered gluten the causal agent. Following the Salerno Experts' Criteria, they underwent a double-blind, placebo controlled trial with gluten vs placebo. A mean value during gluten ingestion >30% of the value during placebo was considered as indicative of gluten sensitivity. Results: After blinded administration of gluten, 13 out of 25 (52%) patients showed an increase in the severity of abdominal pain, and 11 out of 25 (44%) showed an increase in the severity of abdominal bloating. Considering these two symptoms together, in 16 patients out of 25 (64%), blinded gluten administration induced an increase of abdominal pain and/or bloating. The ALCAT 5 test proved to be positive in 20 and negative in 5 patients. In sixteen patients out of 25 the result of ALCAT 5 agreed with the double-blind trial (64%). In particular, both tests were positive in 14 patients and negative in 2. Conclusions: In this subgroup of patients, ALCAT 5 could be used to support the clinical suspicion of the presence of NCGS and to address these patients to a blinded gluten challenge.
Article
Background/objectives: Adherence to gluten-free diet in self reported non-coeliac gluten sensitive subjects is scarcely researched. Objectives of the study were to compare dietary adherence in coeliac disease (CD) subjects and in non-coeliac gluten sensitive (NCGS) subjects, and to estimate gluten exposure based on weighed food records and analysis of gluten content in selected food items. Subjects/methods: Twenty-three subjects with biopsy verified CD on a gluten-free diet and 34 HLA-DQ2(+) NCGS subjects on a self-instituted gluten-free diet were enrolled. The latter group was under investigation of CD. Dietary adherence was assessed by frequency questionnaire and structured forms supplied by weighed food records. For the analyses of food samples, the sandwich R5-ELISA, Ridascreen(®) Gliadin competitive method was used. Results: There was no difference in dietary adherence between CD and NCGS subjects (83% vs 68%, p = 0.21). NCGS subjects were mainly self-educated in gluten-free diet compared to CD subjects (91% and 39%, respectively, p < 0.001). In non-adherent subjects, there was no difference in gluten exposure between CD and NCGS (10 vs 138 mg/day, p = 0.83). There was no difference in BMR-factor between CD and NCGS subjects, or between adherent and non-adherent subjects. Conclusions: Both CD and NCGS subjects were largely adherent, and adherence did not differ between the groups. Gluten exposure varied greatly, and some CD and NCGS subjects reached gluten intake above 500 mg/day, which might have considerable health effects on the individual, especially in case of coeliac disease.
Article
Immune‐mediated disorders affecting the gastrointestinal (GI) tract may compromise GI integrity, interfere with the absorption of nutrients and cause bleeding and inflammation. All these features contribute to the pathogenesis of anaemia, the most prevalent extra‐intestinal manifestation of immune‐mediated GI disorders. Anaemia is most commonly due to iron deficiency and/or inflammation, but vitamin deficiencies and, more infrequently, autoimmune haemolysis or drug‐induced myelosuppression can be involved. Here we address several issues related to the differential diagnosis and treatment of anaemia in immune‐mediated GI disorders, giving particular relevance to the problem of iron deficiency anaemia associated with inflammation. It is emphasized how, in most cases, anaemias due to iron or vitamin deficiencies are best treated by parenteral administration of the deficient factor(s), and how the available high dose intravenous (IV) iron formulations can reduce ambulatory and social costs of IV iron supplementation, while improving patient's compliance to treatment. Actual and future treatment possibilities for anaemia of inflammation, involving the use of erythropoiesis stimulating agents, biologicals and hepcidin inhibitors are discussed.
Article
Background Celiac disease (CD) is a common gastrointestinal pathology; however, prevalence and comorbidities are unknown in collegiate athletics. Hypotheses (1) Athletes will have similar odds of CD as general population estimates (approximately 1 in 141) based on self-report and signs and symptoms, (2) athletes scoring higher on the Celiac Symptom Index (CSI) will have lower self-reported quality of life (QoL), (3) athletes scoring higher on the CSI will have higher depression scores, and (4) athletes scoring higher on the CSI will have higher perceived stress scores. Study Design Epidemiological cross-sectional study. Level of Evidence Level 4. Methods The CSI, WHO Quality of Life-BREF, Beck Depression Inventory, and Perceived Stress Scale were used to assess patients’ signs and symptoms of CD and psychosocial measures/QoL in male and female National Collegiate Athletic Association (all divisions) athletes (N = 141). Participants also self-reported a formal diagnosis of CD. Chi-square analyses determined CD prevalence. Odds ratios determined risk for either being diagnosed with CD or reporting more symptoms than the general population. Correlational analyses determined whether symptoms correlated with QoL and psychosocial measures. Results Athletes were 3.85 times (95% CI, 0.42-34.89) more likely to report a CD diagnosis and were 18.36 times (95% CI, 2.40-140.48) more likely to report a high degree of CD symptoms than the general population. Athletes with more symptoms had worse physical, psychological, social, and environmental QoL indicators and higher depression and perceived stress scores. Conclusion Athletes may be a higher risk population for experiencing CD and report greater signs/symptoms compared with general population estimates. Additionally, athletes with higher CD symptom scores also reported poorer QoL. Clinical Relevance Allied health care professionals should be aware of the diversity of CD symptoms and be prepared to refer athletes when gastrointestinal symptoms persist to ensure proper care and unhampered performance.
Article
Purpose The purpose of our study is to investigate the delay in diagnosis of patients with biopsy-proven celiac disease in those who present with gastrointestinal complaints vs non-gastrointestinal complaints at our tertiary care center. Celiac disease is an autoimmune disorder which affects approximately 1% of the population worldwide. Celiac disease can have variable clinical presentations characterized by either predominately gastrointestinal symptoms or may present without any gastrointestinal symptom. Methods We retrospectively reviewed 687 adult patients’ charts who carried the diagnosis of celiac disease. Patients included had biopsy-proven celiac disease and were categorized based on presence or absence of gastrointestinal symptoms prior to their diagnosis. Results 101 patients with biopsy-proven celiac disease met inclusion criteria. 52 patients presented with gastrointestinal symptoms and 49 had non-gastrointestinal complaints. Results from Mann-Whitney statistical analysis showed a median delay in diagnosis of 2.3 months for gastrointestinal symptoms group and 42 months for non-gastrointestinal group ( P<0.001). 43.2% patients with non-gastrointestinal symptoms had abnormal thyroid-stimulating hormone (TSH) as opposed to 15.5% in the gastrointestinal symptom group (P=0.004). Of patients with non-gastrointestinal symptoms, 69.4% had anemia compared to 11.5% of gastrointestinal symptom group (P<0.001). The majority of patients in the non-gastrointestinal symptom group 68% were noted to have abnormal bone density scans compared to 41% in the gastrointestinal symptom group. No gender differences were noted on Chi square analysis between the two groups (p=0.997). Conclusions Although there is growing awareness of celiac disease, the delay in diagnosis for patients without gastrointestinal symptoms remains prolonged, with an average delay of 3.5 years.
Article
Background: The condition non-coeliac gluten sensitivity (NCGS) is clinically similar to coeliac disease, but lack objective diagnostic criteria. Symptom relief on gluten-free diet followed by gluten containing food challenge may confirm the condition in clinical settings. Aim: To describe the results of an open bread challenge in patients with suspected NCGS, and to compare the results with recently suggested cut-offs for symptom change. Material and methods: Fifty-six patients (12 males) self-instituted on gluten-free diet with negative coeliac disease diagnostics were examined for NCGS by an open bread challenge. Symptoms were reported by Gastrointestinal Symptom Rating Scale, IBS-version (GSRS-IBS) and visual analogue scale (VAS). Results were retrospectively compared to the Salerno and Monash cut-offs for symptom change. Results: Forty-seven patients were diagnosed with NCGS. Total GSRS-IBS score and overall symptoms by VAS increased significantly in NCGS (p < .001), but not in non-NCGS patients (p < .12 and p = .08, respectively). Total GSRS-IBS challenge score and overall symptoms by VAS were significantly higher in NCGS than in non-NCGS patients (53 vs. 37, p = .004 and 76 vs. 39 mm, p = .02, respectively). Applying the Salerno and Monash cut-offs, 63 and 75% would be classified with NCGS, respectively. According to total GSRS–IBS absolute agreement was lowest between clinician’s diagnosis and Salerno cut-off (63%) and highest between Salerno and Monash cut-offs (88%). Conclusion: Clinician diagnosed 85% with NCGS. The proportion of NCGS was lower according to the Salerno and Monash cut-offs. The Salerno cut-off should be the starting point for a common definition of symptom change.
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In contrast to coeliac disease (CD), the mechanism behind non-coeliac gluten sensitivity (NCGS) is unclear. The aims of the study were to measure the presence of somatization, personality traits, anxiety, depression, and health-related quality of life in NCGS individuals compared with CD patients and healthy controls, and to compare the response to gluten challenge between NCGS and CD patients. We examined 22 CD patients and 31 HLA-DQ2+ NCGS patients without CD, all on a gluten-free diet. All but five CD patients were challenged orally for 3 days with gluten; symptom registration was performed during challenge. A comparison group of 40 healthy controls was included. Patients and healthy controls completed questionnaires regarding anxiety, depression, neuroticism and lie, hostility and aggression, alexithymia and health locus of control, physical complaints, and health-related quality of life. The NCGS patients reported more abdominal (p = 0.01) and non-abdominal (p < 0.01) symptoms after gluten challenge than CD patients. There were no significant differences between CD and NCGS patients regarding personality traits, level of somatization, quality of life, anxiety, and depressive symptoms. The somatization level was low in CD and NCGS groups. Symptom increase after gluten challenge was not related to personality in NCGS patients. NCGS patients did not exhibit a tendency for general somatization. Personality and quality of life did not differ between NCGS and CD patients, and were mostly at the same level as in healthy controls. NCGS patients reported more symptoms than CD patients after gluten challenge.
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The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print. www.amjgastro.com, *2007 Journal Citation Report (Thomson Reuters, 2008)
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Objective The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten. Design A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo and phone conferences. In addition to ‘CD’, the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies. Results CD was defined as ‘a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals’. Classical CD was defined as ‘CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.’ ‘Gluten-related disorders’ is the suggested umbrella term for all diseases triggered by gluten and the term gluten intolerance should not to be used. Other definitions are presented in the paper. Conclusion This paper presents the Oslo definitions for CD-related terms.
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INTODUCTION: K562(S) agglutination has been used as a rapid and economic tool for the in vitro screening of the toxicity of cereal fractions and prolamins in celiac disease (CD). A strict correlation has been reported between the toxicity of cereals and cereal fractions for celiac patients and their ability to agglutinate K562(S) cells. Whether this specificity of K562(S)-cell agglutination is caused by the activation of the same pathogenic events triggered by toxic cereal fractions in CD intestine or simply represents a bystander event of gluten toxicity is, however, unknown. K562(S) cells were incubated in vitro with the peptic-tryptic digest of wheat gliadin. The agglutination of K562(S) cells by wheat gliadin peptides is orchestrated by a cascade of very early events occurring at the K562(S)-cell surface similar to those occurring at the intestinal epithelial surface. They involve a rapid increase in intracellular calcium levels that activate tissue transglutaminase (TG2), leading to a rapid actin reorganization that is pivotal in driving cell agglutination. These specific effects of toxic cereals are phenocopied by the gliadin-derived peptide p31-43, which orchestrates the activation of innate response to gliadin in CD. Our study provides the rationale for the extensive use of K562(S)-cell agglutination as a valuable tool for screening cereal toxicity.
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To evaluate the possible association between celiac disease (CD) and/or gluten sensitivity (GS) and autism spectrum disorder (ASD). Occurrences of CD were determined in a group of children and adolescents affected by ASD and, conversely, occurrences of ASD were assessed in a group of biopsy-proven celiac patients. To detect the possible existence of GS, the levels of antigliadin antibodies in ASD patients were assessed and compared with the levels in a group of non-celiac children. The prevalence of CD or GS in ASD patients was not greater than in groups originating from the same geographical area. Similarly the prevalence of ASD was not greater than in a group of biopsy-proven CD patients. No statistically demonstrable association was found between CD or GS and ASD. Consequently, routine screening for CD or GS in all patients with ASD is, at this moment, neither justified nor cost-effective.
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Several animal models have been recently developed to recapitulate various components of the complex process that is celiac disease. In addition to the increasing diversity of murine models there are now monkey models of celiac disease. Mouse strains and protocols have been developed that are now just beginning to address the complex interactions among the innate and adaptive immune responses to gluten, as well as gluten-dependent autoimmunity in celiac disease. The most important conclusion that these models have provided us with so far is that while all three components (innate gluten sensitivity, adaptive gluten sensitivity, and autoimmunity) are independent phenomena, all are necessary for celiac disease to develop.
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Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten. Gluten-sensitive individuals (GS) cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in CD, but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities. By studying and comparing mucosal expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in CD compared with GS, we sought to better understand the similarities and differences between these two gluten-associated disorders. CD, GS and healthy, gluten-tolerant individuals were enrolled in this study. Intestinal permeability was evaluated using a lactulose and mannitol probe, and mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity. Unlike CD, GS is not associated with increased intestinal permeability. In fact, this was significantly reduced in GS compared with controls (P = 0.0308), paralleled by significantly increased expression of claudin (CLDN) 4 (P = 0.0286). Relative to controls, adaptive immunity markers interleukin (IL)-6 (P = 0.0124) and IL-21 (P = 0.0572) were expressed at higher levels in CD but not in GS, while expression of the innate immunity marker Toll-like receptor (TLR) 2 was increased in GS but not in CD (P = 0.0295). Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in GS relative to controls (P = 0.0325) and CD patients (P = 0.0293). This study shows that the two gluten-associated disorders, CD and GS, are different clinical entities, and it contributes to the characterization of GS as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.
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Investigation of uncertain celiac disease (CD) in patients already on a gluten-free diet (GFD) is difficult. We evaluated HLA-DQ2-gliadin tetramers for detection of gluten-specific T cells in peripheral blood and histological changes in the duodenum after a short gluten challenge as a diagnostic tool. HLA-DQ2+ individuals on a GFD for at least 4 weeks were investigated; 35 with uncertain diagnosis, 13 CD patients, and 2 disease controls. All participants had a challenge with four slices of gluten-containing white bread, daily for 3 days (d1-d3). An esophagogastroduodenoscopy with biopsy sampling was done on d0 and d4. Biopsies were scored according to revised Marsh criteria. Peripheral blood CD4+ T cells were isolated, stained with HLA-DQ2-gliadin peptide tetramers, and analyzed by flow cytometry on d0 and d6. After challenge, a positive tetramer test was seen in 11/13 CD patients. Four of these subjects also showed typical histological changes on challenge. Of the 35 patients with uncertain diagnosis, 3 were diagnosed with CD. Two of these three patients had both positive tetramer staining and histological changes in biopsies after challenge. Tetramer staining for gluten-specific T cells is a sensitive method in detecting an immune response in CD patients after a short gluten challenge. The prevalence of CD in the group with self-prescribed GFD was about 10%.
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Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism. A double-blind, randomized, placebo-controlled rechallenge trial was undertaken in patients with irritable bowel syndrome in whom celiac disease was excluded and who were symptomatically controlled on a gluten-free diet. Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. Symptoms were evaluated using a visual analog scale and markers of intestinal inflammation, injury, and immune activation were monitored. A total of 34 patients (aged 29-59 years, 4 men) completed the study as per protocol. Overall, 56% had human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high. Of 19 patients (68%) in the gluten group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation). On a visual analog scale, patients were significantly worse with gluten within 1 week for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001). Anti-gliadin antibodies were not induced. There were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with or without DQ2/DQ8. "Non-celiac gluten intolerance" may exist, but no clues to the mechanism were elucidated.
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In the past few years, the number of celiac disease diagnoses not confirmed at the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, a tertiary referral centre, was particularly high. Therefore, a decision was made to investigate the reasons why these diagnoses were wrong and by whom they had been made. The clinical histories of all celiac patients referred to the centre were re-evaluated. Between December 1998 and January 2007, 614 patients who were diagnosed at other institutions and presumed to be affected by celiac disease attended the tertiary referral outpatient clinic. The histological and serological results allowed for confirmation the diagnosis in 434 patients. In the remaining 180 patients, the initial diagnosis of celiac disease could not be confirmed; therefore, the patients were re-investigated. After re-evaluation, the diagnosis of celiac disease was confirmed in only 61 of these 180 cases. The reasons for incorrect initial diagnosis were analyzed. A mere 80% correct diagnosis rate is a very disappointing result. Although it should be obvious that celiac disease must be investigated with duodenal biopsies and celiac antibody testing, this well-known strategy is not always followed, probably resulting in an incorrect diagnosis.
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Celiac disease (CD) and schizophrenia have approximately the same prevalence, but epidemiologic data show higher prevalence of CD among schizophrenia patients. The reason for this higher co-occurrence is not known, but the clinical knowledge about the presence of immunologic markers for CD or gluten intolerance in schizophrenia patients may have implications for treatment. Our goal was to evaluate antibody prevalence to gliadin (AGA), transglutaminase (tTG), and endomysium (EMA) in a group of individuals with schizophrenia and a comparison group. AGA, tTG, and EMA antibodies were assayed in 1401 schizophrenia patients who were part of the Clinical Antipsychotic Trials of Intervention Effectiveness study and 900 controls. Psychopathology in schizophrenia patients was assessed using the Positive and Negative Symptoms Scale (PANSS). Logistic regression was used to assess the difference in the frequency of AGA, immunoglobulin A (IgA), and tTG antibodies, adjusting for age, sex, and race. Linear regression was used to predict PANSS scores from AGA and tTG antibodies adjusting for age, gender, and race. Among schizophrenia patients, 23.1% had moderate to high levels of IgA-AGA compared with 3.1% of the comparison group (χ(2) = 1885, df = 2, P < .001.) Moderate to high levels of tTG antibodies were present in 5.4% of schizophrenia patients vs 0.80% of the comparison group (χ(2) = 392.0, df = 2, P < .001). Adjustments for sex, age, and race had trivial effects on the differences. Regression analyses failed to predict PANSS scores from AGA and tTG antibodies. Persons with schizophrenia have higher than expected titers of antibodies related to CD and gluten sensitivity.
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The understanding of the pathogenesis of celiac disease has made huge advances in recent years. The disease is caused by an inappropriate immune response to dietary gluten proteins. This immune response is controlled by CD4(+) T cells in the lamina propria that recognize gluten peptides in the context of disease predisposing HLA-DQ2 and HLA-DQ8 molecules.(1, 2) These T cells are specific for proline- and glutamine-rich gluten peptides that are resistant to proteolysis and that have been become deamidated by the enzyme transglutaminase 2 (TG2). Strikingly, celiac disease patients produce antibodies to this same enzyme when exposed to dietary gluten. Here we discuss how the new insight in the pathogenesis has lead to development of new diagnostics and nourished research into novel treatments.
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The Rome diagnostic criteria for the functional bowel disorders and functional abdominal pain are used widely in research and practice. A committee consensus approach, including criticism from multinational expert reviewers, was used to revise the diagnostic criteria and update diagnosis and treatment recommendations, based on research results. The terminology was clarified and the diagnostic criteria and management recommendations were revised. A functional bowel disorder (FBD) is diagnosed by characteristic symptoms for at least 12 weeks during the preceding 12 months in the absence of a structural or biochemical explanation. The irritable bowel syndrome, functional abdominal bloating, functional constipation, and functional diarrhea are distinguished by symptom-based diagnostic criteria. Unspecified FBD lacks criteria for the other FBDs. Diagnostic testing is individualized, depending on patient age, primary symptom characteristics, and other clinical and laboratory features. Functional abdominal pain (FAP) is defined as either the FAP syndrome, which requires at least six months of pain with poor relation to gut function and loss of daily activities, or unspecified FAP, which lacks criteria for the FAP syndrome. An organic cause for the pain must be excluded, but aspects of the patient's pain behavior are of primary importance. Treatment of the FBDs relies upon confident diagnosis, explanation, and reassurance. Diet alteration, drug treatment, and psychotherapy may be beneficial, depending on the symptoms and psychological features.
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Celiac disease (CD) is an increasingly diagnosed enteropathy (prevalence, 1:200-1:300) that is induced by dietary exposure to wheat gliadins (as well as related proteins in rye and barley) and is strongly associated with HLA-DQ2 (alpha1*0501, beta1*0201), which is present in over 90% of CD patients. Because a variety of gliadin peptides have been identified as epitopes for gliadin-specific T-cell clones and as bioactive sequences in feeding studies and in ex vivo CD intestinal biopsy challenge, it has been unclear whether a 'dominant' T-cell epitope is associated with CD. Here, we used fresh peripheral blood lymphocytes from individual subjects undergoing short-term antigen challenge and tissue transglutaminase-treated, overlapping synthetic peptides spanning A-gliadin to demonstrate a transient, disease-specific, DQ2-restricted, CD4 T-cell response to a single dominant epitope. Optimal gamma interferon release in an ELISPOT assay was elicited by a 17-amino-acid peptide corresponding to the partially deamidated peptide of A-gliadin amino acids 57-73 (Q65E). Consistent with earlier reports indicating that host tissue transglutaminase modification of gliadin enhances gliadin-specific CD T-cell responses, tissue transglutaminase specifically deamidated Q65 in the peptide of A-gliadin amino acids 56-75. Discovery of this dominant epitope may allow development of antigen-specific immunotherapy for CD.
Article
We examined Dohan's hypothesis that schizophrenia is associated with the absorption of "exorphins" contained in gluten and casein. In addition, because of the work of Reichelt et al. (Reichelt, K.L., Saelid, G., Lindback, J. and Orbeck, H. (1986) Biological Psychiatry 21:1279-1290) and Rodriguez et al. (Rodriguez, Trav, A.L., Barreiro Marin, P., Galvez, Borrero, I.M., del Olmo Romero-Nieva, F. and Diaz Alvarez, A. (1994) Journal of Nervous and Mental Disease Aug; 182(8): 478-479), we carried out similar studies on a group of children with autism. In both syndromes we found similar patterns of peptide containing peaks (Ninhydrin positive) after molecular screening with Sephadex G-15. Immunoglobulin assay of IgA and IgG against glia-din and casein in serum was done. High titer IgG antibodies to gliadin were found in 87% of autistic and 86% of schizophrenic patients and high titer IgG antibodies to bovine casein were found in 90% of autistic and in 93% of schizophrenic patients. High titer IgA antibodies to gluten or casein were found in 30% of children with autism while in schizophrenic patients 86% had elevated IgA antibodies to gluten and 67% to casein; some normal children and adults have these antibodies but only in trace amounts. When schizophrenic patients were treated with dialysis or a gluten-casein free diet, or both (Cade, R., Wagemaker, H., Privette, R.M., Fregly, M., Rogers, J. and Orlando, J. (1990) Psychiatry: A World Prespective 1: 494-500) peptiduria and Brief Psychiatric Rating Scores fell while abnormal behavior diminished. A gluten-casein free diet was accompanied by improvement in 81% of autistic children within 3 months in most of the behavior categories. Our data provide support for the proposal that many patients with schizophrenia or autism suffer due to absorption of exorphins formed in the intestine from incomplete digestion of gluten and casein.
Article
A total of 104 patients with sporadic cerebellar ataxia were tested for antigliadin and antiendomysium antibodies. Twelve individuals (11.5%) with gluten sensitivity underwent duodenal biopsy and extensive clinical, electrophysiological, neuropsychological, radiological and laboratory investigations including human leucocyte antigen (HLA) typing. Two patients showed typical changes of gluten-sensitive enteropathy with crypt hyperplasia and mucosal flattening. In five patients, the intraepithelial lymphocyte count was elevated. Sporadic ataxia with gluten sensitivity was found to be tightly linked to the HLA DQB1*0201 haplotype (70%). Neurological symptoms were not related to hypovitaminosis or inflammatory CSF changes. The clinical syndrome was dominated by progressive cerebellar ataxia with ataxia of stance and gait (100%), dysarthria (100%) and limb ataxia (97%). Oculomotor abnormalities were gaze-evoked nystagmus (66.7%), spontaneous nystagmus (33.3%), saccade slowing (25%) and upward gaze palsy (16.7%). Extracerebellar features also included deep sensory loss (58.3%), bladder dysfunction (33.3%) and reduced ankle reflexes (33.3%). In accordance with clinical findings, electrophysiological investigations revealed prominent axonal neuropathy with reduced amplitudes (50%) and abnormal evoked potentials (58.3%). On neuropsychological testing, patients presented with moderate verbal memory and executive dysfunction. All patients had evidence of cerebellar atrophy on MRI. We conclude that sporadic ataxia may be associated with positive antibodies against gliadin. Nevertheless, mucosal pathology does not represent an obligatory condition of ataxia with gluten sensitivity. The fact that the disease is strongly associated with the same HLA haplotypes found in coeliac disease not only demonstrates coeliac disease and ataxia with gluten sensitivity to be part of the same disease entity but supports the hypothesis of an immunological pathogenesis of cerebellar degeneration.
Article
OBJECTIVE:We have undertaken a study to assess the efficiency of serological tests in the diagnosis of celiac disease (CD) during the period January 1, 1994 to January 7, 1997. Our aim was to evaluate the sensitivity of IgA antiendomysium (EMA) and IgA antigliadin (AGA) with regard to the degree of histological abnormality in biopsy specimens of small intestine in untreated celiac disease patients and first-degree relatives.METHODS:The study population comprised 101 cases: 85 untreated celiac patients and 16 first-degree relatives with a mean age of 42 yr (range, 2–76 yrs). Sixteen of 85 were excluded from study because they did not satisfy the study or diagnostic criteria of CD. EMA and AGA have been compared with the degree of villous atrophy (VA) in 69 celiac patients and 16 relatives according to the Marsh criteria of 1992. We divided the Marsh III histology into three subgroups as follows: Marsh IIIa (partial VA), Marsh IIIb (subtotal VA), and Marsh IIIc (total villous atrophy).RESULTS:The specificity and positive predictive value of EMA for CD was excellent, because all EMA-positive patients (n = 42) were diagnosed with CD. The sensitivity of EMA, however, differed between CD subgroups; in patients with total VA, the sensitivity of EMA was 100% (17/17). However, in patients with partial VA (Marsh IIIa), the sensitivity of EMA was disappointing, only 9/29 (31%). Three of 72 celiacs with Marsh IIIb and Marsh IIIc had IgA deficiency and were excluded from the study. Elevated AGA has been detected in the sera of 39 of 69 (62%) patients. A combination of EMA and AGA tests showed a sensitivity of 76% (53/69). None of 16 first-degree relatives with Marsh I-II had positive EMA.CONCLUSIONS:Interpretation of negative serology needs great awareness. Although EMA sensitivity in total villous atrophy is excellent, in partial villous atrophy the sensitivity of EMA appears to be disappointing. Our experience shows that EMA and AGA have only limited value in screening programs for CD.
Article
Background & aims We sought to establish the level of knowledge of celiac disease (CD) and gluten sensitivity (GS) among the general public and chefs, and to compare dining habits of people with CD and the general public. Methods Surveys assessing knowledge of CD and GS as well as dining habits were administered through an Internet survey tool or face-to-face. The chef survey also assessed training/education. Results Among 861 persons from the general public 47% had heard of CD, 67% of GS and 88% of peanut allergy. Chefs were more likely than the general public to have heard of CD (77% vs. 47%, p < 0.0001), though greater proportions in both groups had heard of GS (89% vs. 67%, p < 0.0001). 63% of patients (n = 790) reported that they avoid restaurants because of the gluten-free diet and ate take-out food and restaurant food significantly less often than the general public. Trained chefs had more knowledge than untrained chefs (83% vs. 52%, p < 0.0001). There was a direct relationship between the average check price and chefs’ awareness (<$25: 64% vs. >$65: 94%, p < 0.0001). Conclusions Awareness of gluten-related issues was prominent. Surprisingly, both the public and chefs were more likely to have heard of GS than CD. Most with CD avoid restaurants, and eat outside the home less frequently than the general public. Knowledge of CD among chefs exceeds that of the general public, but varies considerably.
Article
We note Dr Wills’ and Dr Unsworth’s continued scepticism at the concept of gluten ataxia in the face of overwhelming evidence in its support. We have proposed that IgG antigliadin antibodies are currently the best marker of the whole spectrum of gluten sensitivity although they are not specific for gluten‐sensitive enteropathy. We hope that a better marker of neurological manifestations of gluten sensitivity will come with the identification of the antibodies recognizing neuronal epitopes, such as those on Purkinje cells identified by antibodies in patients with gluten ataxia. This would be analogous to the antiendomysium antibody in cases with gluten‐sensitive enteropathy or epidermal …
Article
To characterize the serological pattern of gluten sensitivity (GS) and to compare it with that found in celiac disease. GS has recently been identified as a new clinical entity included in the spectrum of gluten-related disorders, but it is still lacking of diagnostic markers. Sera from 78 patients with GS and 80 patients with celiac disease were retrospectively assessed for immunoglobulin (Ig)G/IgA antigliadin antibodies (AGA), IgG deamidated gliadin peptide antibodies (DGP-AGA), IgA tissue transglutaminase antibodies (tTGA), and IgA endomysial antibodies (EmA). IgG AGA were positive in 56.4% of GS patients and in 81.2% of celiac patients, with high antibody titers in both groups. IgA AGA were detected in 7.7% of GS patients and in 75% of celiac patients, showing lower enzyme-linked immunosorbent assay activities in GS than those found in celiac disease. Only 1 of the 78 patients with GS was positive for IgG DGP-AGA (detected in 88.7% of patients with celiac disease). IgA tTGA and IgA EmA were negative in all GS patients, whereas their positivity in celiac patients was 98.7% and 95%, respectively. Patients with GS displayed a variegated clinical picture with intestinal and extraintestinal symptoms (abdominal pain, bloating, diarrhea, constipation, foggy mind, tiredness, eczema/skin rash, headache, joint/muscle pain, numbness of legs/arms, depression, and anemia) together with normal or mildly abnormal small intestinal mucosa. The serological pattern of GS is characterized by IgG AGA positivity in more than half of cases associated to IgA AGA in a few patients, but without EmA, tTGA, and DGP-AGA, which are the specific markers of celiac disease.
Article
Irritable bowel syndrome (IBS) imposes significant clinical and economic burdens. We aimed to characterize practice patterns for patients with IBS in a large health maintenance organization, analyzing point of diagnosis, testing, comorbidities, and treatment. Members of Kaiser Permanente Northern California who were diagnosed with IBS were matched to controls by age, sex, and period of enrollment. We compared rates of testing, comorbidities, and interventions. From 1995-2005, IBS was diagnosed in 141,295 patients (mean age, 46 years; standard deviation, 17 years; 74% female). Internists made 68% of diagnoses, gastroenterologists 13%, and others 19%. Lower endoscopy did not usually precede IBS diagnosis. Patients with IBS were more likely than controls to have blood, stool, endoscopic, and radiologic tests and to undergo abdominal or pelvic operations (odds ratios, 1.5-10.7; all P < .0001). Only 2.7% were tested for celiac disease, and only 1.8% were eventually diagnosed with inflammatory bowel disease. Chronic pain syndromes, anxiety, and depression were more common among IBS patients than among controls (odds ratios, 2.7-4.6; all P < .0001). Many patients with IBS were treated with anxiolytics (61%) and antidepressants (55%). Endoscopic and radiologic testing was most strongly associated with having IBS diagnosed by a gastroenterologist. Psychotropic medication use was most strongly associated with female sex. In a large, managed care cohort, most diagnoses of IBS were made by generalists, often without endoscopic evaluation. Patients with IBS had consistently higher rates of testing, chronic pain syndromes, psychiatric comorbidity, and operations than controls. Most patients with IBS were treated with psychiatric medications.
Article
The specificity of the conventional gliadin antibody test is considered low. We explored whether gliadin antibody(AGA)-positivity without tissue transglutaminase antibodies (tTGA) is persistent in the elderly population and whether such positivity indicates overt or potential coeliac disease in genetically predisposed individuals. AGA and tissue transglutaminase antibody were measured in 2089 elderly individuals twice with a three-year interval. AGA-positive but tissue transglutaminase antibody-negative subjects with coeliac-type human leucocyte antigen (HLA) were examined and underwent gastroduodenal endoscopy (cases). Small-bowel mucosal villous morphology and densities of CD3+ and γδ+ intraepithelial lymphocytes and the occurrence of tissue transglutaminase-specific IgA deposits were analysed. Randomly selected persistently AGA-negative age- and sex-matched subjects served as controls. AGA-positivity was persistent in 81% of those initially positive. Amongst the 49 clinically studied and 36 endoscopied cases only one (2.8%) had coeliac disease. Many (54%) showed signs of inflammation in the biopsy, without villous atrophy. Coeliac-type HLA was not over-represented in the persistently AGA-positive compared to the general population. Persistently AGA-positive coeliac-type HLA-positive subjects had more gastrointestinal symptoms than AGA-negative controls. AGA-positivity is often persistent. Overt coeliac disease is seldom found behind persistent AGA-positivity, but this characteristic is associated with mucosal inflammation and gastrointestinal symptoms at least in HLA-positive individuals.
Article
Food allergy is becoming an increasingly common diagnosis. Because of this increase in prevalence, it is imperative that physicians evaluating patients with possible adverse reactions to foods understand the currently available assays and how they should best be used to accurately diagnose the disease. Simple tests such as skin prick testing (SPT) and serum food-specific IgE testing are the most commonly used diagnostic tests to evaluate for IgE-mediated food reactions. However, these tests, which measure sensitization and not clinical allergy, are not without pitfalls, and their utility must be appreciated to avoid over- and underdiagnosis. Although the physician-supervised oral food challenge remains the gold standard for food allergy diagnosis, a careful medical history paired with SPT and serum food-specific IgE testing often can provide a reliable diagnosis. In this review, we examine the usefulness and pitfalls of SPT and serum food-specific IgE levels, as well as examine atopy patch testing and other emerging tests, such as component-resolved diagnostics and the basophil activation test. Finally, we describe the use of the double-blind, placebo-controlled oral food challenge as the current gold standard for food allergy diagnosis.
Article
Increased immune sensitivity to gluten has been reported in schizophrenia. However, studies are inconsistent about this association. The sample of 471 individuals included 129 with recent-onset psychosis, 191 with multi-episode schizophrenia, and 151 controls. Immunoglobulin (Ig)G and IgA antibodies to gliadin and to tissue transglutaminase, and IgG antibodies to deamidated gliadin were measured. Quantitative levels of antibodies in the psychiatric groups were compared with controls. All participants were categorized as to whether their levels of antibodies met standardized cutoffs for celiac disease. HLA DQ2 and HLA DQ8 alleles were detected by real-time polymerase chain reaction. Individuals with recent-onset psychosis had increased levels of IgG (odds ratio [OR] 5.50; 95% confidence interval [CI] 2.65-11.42) and IgA (OR 2.75; 95% CI 1.31-5.75) antibodies to gliadin compared with control subjects. Individuals with multi-episode schizophrenia also had significantly increased levels of IgG antibodies to gliadin (OR 6.19; 95% CI 2.70-14.16). IgG antibodies to deamidated gliadin and IgA antibodies to tissue transglutaminase were not elevated in either psychiatric group, and fewer than 1% of individuals in each of the groups had levels of these antibodies predictive of celiac disease. There were no significant differences in the distribution of the HLA DQ2/8 alleles among the groups. Individuals with recent-onset psychosis and with multi-episode schizophrenia who have increased antibodies to gliadin may share some immunologic features of celiac disease, but their immune response to gliadin differs from that of celiac disease.
Article
A link between celiac disease and schizophrenia has been postulated for several years, based primarily on reports of elevated levels of antibody to gliadin in patients. We sought to examine the proposed connection between schizophrenia and celiac disease by characterizing the molecular specificity and mechanism of the anti-gliadin immune response in a subset of individuals with schizophrenia. Blood samples from individuals with schizophrenia and elevated anti-gliadin antibody titer were examined for celiac disease-associated biomarkers, including antibodies to transglutaminase 2 (TG2) enzyme and deamidated gliadin peptides, as well as the HLA-DQ2 and -DQ8 MHC genes. The anti-gliadin antibody response was further characterized through examination of reactivity towards chromatographically separated gluten proteins. Target proteins of interest were identified by peptide mass mapping. In contrast to celiac disease patients, an association between the anti-gliadin immune response and anti-TG2 antibody or HLA-DQ2 and -DQ8 markers was not found in individuals with schizophrenia. In addition, the majority of individuals with schizophrenia and anti-gliadin antibody did not exhibit antibody reactivity to deamidated gliadin peptides. Further characterization of the antibody specificity revealed preferential reactivity towards different gluten proteins in the schizophrenia and celiac disease groups. These findings indicate that the anti-gliadin immune response in schizophrenia has a different antigenic specificity from that in celiac disease and is independent of the action of transglutaminase enzyme and HLA-DQ2/DQ8. Meanwhile, the presence of elevated levels of antibodies to specific gluten proteins points to shared immunologic abnormalities in a subset of schizophrenia patients. Further characterization and understanding of the immune response to gluten in schizophrenia may provide novel insights into the etiopathogenesis of specific disease phenotypes.
Article
The double-blind, placebo-controlled food challenge (DBPCFC) is widely considered as the 'gold standard' for the diagnosis of food allergy. However, in adult patients, this procedure is rather rarely performed outside the academic context. This review article aims to reappraise the pros and cons of DBPCFC and to elicit some critical thoughts and discussions about the real indications of this diagnostic procedure in adult patients in everyday practice. There are many data showing that the DBPCFC poses a number of critical problems that are difficult to overcome in normal outpatient clinics and hospitals, and that are generally not addressed in most articles dealing with this issue. Performing DBPCFC poses a number of practical problems and has several pitfalls, which make its routine use in normal clinical settings generally impossible. This review article shows that the need for this procedure in adult patients seems in effect very little and specifies new, more limited indications to its use in everyday practice. Further, it suggests a role for the open challenge, which lacks several of the disadvantages of DBPCFC.
Article
The prevalence of classic autism and autism spectrum disorder (ASD) appears to be on the rise, and to date, there remains no clear etiology or cure. Out of desperation, many families are turning to new therapies and interventions discovered through various media sources and anecdotal reports from other parents. Unfortunately, many of these newer, well-publicized interventions have little empirical support. One of the most popular yet currently scientifically unproven interventions for ASD is the gluten-free, casein-free (GFCF) diet. Clinicians working with families of individuals with ASD are often asked for advice and find themselves unable to offer the most up-to-date and scientifically credible information. This article provides an overview of ASD and the GFCF diet, a summary and critique of current research findings, recommendations for future research, and practical advice for families to use in deciding if a trial of the GFCF diet is in the best interest of their child and family.
Article
Few studies have compared gastrointestinal problems in children with an autism spectrum disorder with and without a history of language regression. A cross-sectional study was conducted with structured interviews in 100 children with autism spectrum disorder, using a gastrointestinal questionnaire and a familial autoimmune questionnaire. By parental report, children with language regression more frequently exhibited an abnormal stool pattern (40% vs 12%, P = 0.006) and had an increased family history of celiac disease or inflammatory bowel disease (24% vs 0%, P = 0.001) and of rheumatoid arthritis (30% vs 11%, P = 0.03). Among 35 children with a family history of autoimmune disease, an abnormal stool pattern was reported more frequently in those with language regression (78% vs 15%, P = 0.001) than in those without. An association was observed between children with language regression, a family history of autoimmune disease, and gastrointestinal symptoms. Additional studies are needed to examine a possible shared autoimmune process.
Article
The sensitivity and specificity of current antihuman tissue transglutaminase (tTG) IgA assays used to detect celiac disease reportedly approach 100%. In addition, the sensitivity of new generation deamidated gliadin peptide (alpha-DGP) antibody assays has also been reported to be similar to the tTG IgA assays. In routine clinical practice, however, the sensitivities and specificities of these tests for diagnosing celiac disease seem to be lower. We analyzed sensitivities and specificities of 4 IgA tTG and 3 deamidated gliadin peptide (alpha-DGP) kits. The performance of 4 tTG IgA assays, A: Inova (Hu red blood cell), B: Binding site (rHu Ag), C: Eurospital (rHu Ag), D: Immco (rHu Ag) and 3 Inova alpha-DGP assays, E: alpha-DGP-IgA, F: alpha-DGP-IgG, and G: alpha-DGP-IgA+G was evaluated using sera from different subsets of celiac disease patients and controls; group 1: active celiac disease n=28, group 2: gluten-free diet n=54, group 3: healthy controls n=40, group 4: disease controls n=57(Crohn's disease n=17, chronic hepatitis n=40). Using the manufacturer's cut-off values, the sensitivities and specificities of different kits ranged from 71.4% to 96.4% and 87.5% to 100%, respectively. When group 1 was compared with disease controls, sensitivities remained the same but specificities decreased. Receiver operating characteristic plot derived cut-off values modified decision thresholds in all assays except kit (G). Kappa analysis demonstrated variable degrees of agreement. All assays demonstrated higher sensitivities for patients with higher grades of villous atrophy. Overall sensitivity was at or below 90%, which is lower than that reported in the literature. Performance of the recombinant and red blood cell antigen-based tTG assays was similar, whereas the alpha-DGP assays demonstrated lower values. Receiver operating characteristic plot derived cut-off values altered test results. Many factors affect the results of these tests and clinicians should be aware of their limitations.
Article
Eight autistic patients with steatorrhoea, hypocalciuria, and alleged behavioural improvements on gluten restriction, were fed ordinary diets plus 20 g gluten/day for 4 weeks. None of the patients had any significant change in body-weight or bowel habit as a result of gluten challenge, nor were any histological abnormalities detected on jejunal biopsy. The data suggest that the steatorrhoea and hypocalciuria seen in some autistic subjects cannot be accounted for by the presence of coeliac disease. Furthermore, these patients should not be confined to gluten-free diets, unless rigorous behavioural studies demonstrate a statistically significant improvement in behaviour as a result of the diet, or deterioration during challenge.