Riccardo Troncone

University of Chicago, Chicago, Illinois, United States

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Publications (330)1473.75 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Celiac disease (CD) represents a spectrum, which includes cases with minor histological abnormalities (potential CD). The aim of this work is to evaluate the contribution of immunohistochemical analysis of duodenal biopsies to the diagnosis of gluten-related minor enteropathy. Duodenal biopsies from 56 untreated CD patients and 56 controls were analyzed for CD3 and γδ intraepithelial lymphocytes number, γδ /CD3 ratio, density of CD25+ lamina propria cells. A discriminant equation was obtained by which 61 more biopsies with normal villous architecture were blindly evaluated. All the immunohistochemical parameters were significantly different between CD and control patients. None of the single parameters showed sufficient specificity for CD. The combination of all four markers resulted in the following discriminant equation: Dscore = (CD3 x 0.06) - (γδ x 0.119) + (CD25 x 0.012) + (γδ /CD3 x 0.131) - 4.709. Using this discriminant score patients were correctly classified as celiac or controls in 97.3% of cases. When this equation was applied to a validation set of 61 patients with normal villous architecture and unknown diagnosis, 92.9% of those with a positive score turned out to be potential celiac patients. However, a normal score did not exclude this condition. Immunohistochemistry represents a very specific tool for the diagnosis of CD, but does lack sensitivity in detecting all potential CD cases.
    Journal of Pediatric Gastroenterology and Nutrition 12/2014; · 2.87 Impact Factor
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    ABSTRACT: Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Undigested gliadin peptides induce innate and adaptive T cell-mediated immune responses. The major mediator of the stress and innate immune response to gliadin peptides (i.e., peptide 31-43, P31-43) is the cytokine interleukin-15 (IL-15). The role of epithelial growth factor (EGF) as a mediator of enterocyte proliferation and the innate immune response has been described. In this paper, we review the most recent literature on the mechanisms responsible for triggering the up-regulation of these mediators in CD by gliadin peptides. We will discuss the role of P31-43 in enterocyte proliferation, structural changes and the innate immune response in CD mucosa in cooperation with EGF and IL-15, and the mechanism of up-regulation of these mediators related to vesicular trafficking. We will also review the literature that focuses on constitutive alterations of the structure, signalling/proliferation and stress/innate immunity pathways of CD cells. Finally, we will discuss how these pathways can be triggered by gliadin peptide P31-43 in controls, mimicking the celiac cellular phenotype.
    International Journal of Molecular Sciences 11/2014; 15(11):20518-20537. · 2.46 Impact Factor
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    ABSTRACT: Although dietary counseling is generally recommended in children with food allergy (FA), its effect on the nutritional status of these patients has not yet been evaluated. Our nonrandomized multicenter prospective intervention study was undertaken to investigate the effects of dietary counseling on children with FA. Anthropometric data, dietary intakes, and laboratory biomarkers of nutritional status were evaluated in children with FA (aged 6 to 36 months) before and after dietary counseling, by multidisciplinary teams composed of pediatricians, dietitians, and nurses. Ninety-one children with FA (49 boys and 42 girls; mean age 18.9 months, 95% CI 16.5 to 21.3) were evaluated; 66 children without FA (41 boys and 25 girls; mean age 20.3 months, 95% CI 17.7 to 22.8) served as controls providing baseline values only. At enrollment, energy and protein intakes were lower in children with FA (91 kcal/kg/day, interquartile range [IQR]=15.1, minimum=55.2, maximum=130.6; and 2.2 g/kg/day, IQR=0.5, minimum=1.5, maximum=2.7, respectively) than in children without FA (96 kcal/kg/day, IQR=6.1, minimum=83.6, maximum=118.0; and 4.6 g/kg/day, IQR=1.2, minimum=2.0, maximum=6.1, respectively; P<0.001). A weight to length ratio <2 standard deviations was more frequent in children with FA than in children without FA (21% vs 3%; P<0.001). At 6 months following dietary counseling, the total energy intake of children with FA was similar to the baseline values of control children. Dietary counseling also resulted in a significant improvement of their anthropometric and laboratory biomarkers of nutritional status. The results of our study support the crucial role of dietary counseling in the clinical management of children with FA.
    Journal of the American Academy of Nutrition and Dietetics 09/2014; · 2.44 Impact Factor
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    ABSTRACT: Celiac disease (CD) is an enteropathy caused by the ingestion of wheat gluten in genetically susceptible individuals. A complete understanding of pathogenic mechanisms in CD has been hindered because of the lack of adequate in vivo models. Herein, we explored the events following the intragastric administration of gliadin and of albumin/globulin fraction (alb/glob) from wheat in HLA-DQ8-transgenic mice (DQ8) treated with indomethacin, an inhibitor of cyclooxygenases (COXs). After a 10-day treatment mice showed a significant reduction of villus height, increased crypt depth, increased number of lamina propria activated macrophages and high basal interferon-γ (IFN-γ secretion in mesenteric lymph nodes all of which were specifically related to gliadin intake whereas alb/glob was unable to induce similar changes. Co-treatment with NS-398, a specific inhibitor of COX-2, also induced the intestinal lesion. Enteropathy onset was further characterized by high levels of oxidative stress markers, similar to CD. The biochemical assessment of the small intestine revealed the specific activation of matrix metalloproteinases 2 and 9 (MMP2/9), a high caspase-3 activity and a significant increase of tissue transglutaminase (tTG) protein levels associated with the intestinal lesion. Notably, after a 30-day treatment enteropathic mice developed serum antibodies toward gliadin (IgA) and tTG (IgG). We concluded that gliadin intake in combination with COX inhibition caused a basal inflammatory status and an oxidative stress condition in the small intestine of DQ8 mice, thus triggering the mucosal lesion and, subsequently, an antigen-specific immunity.
    AJP Gastrointestinal and Liver Physiology 08/2014; . Epub 2014 Jun 12(307(3):):302-312. · 3.65 Impact Factor
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    ABSTRACT: Abstract Several recent reports describe a role of probiotics as a therapeutic approach for celiac disease (CD). Two undigested A-gliadin peptides, P31-43 and P57-68, are central to CD pathogenesis, inducing an innate and an adaptive immune response, respectively. They enter enterocytes and localize to vesicular compartment to induce their toxic/immunogenics effects. In this article, we tested the effect of probiotic Lactobacillus paracasei (LP) CBA L74 (International Depository Accession Number LMG P-24778), its supernatant and LP-fermented cereals on gliadin peptides, P31-43 and P57-68, entrance in Caco-2 cells. Both LP CBA L74 and its supernatant inhibit P31-43 (intensity of fluorescence; FI: 75%) and P57-68 (FI: 50%) entrance in Caco2 cells, indicating that this biological effect is due to some product included in LP CBA L74 supernatant. This effect was present also after fermentation of cereals. This study describes a novel effect of probiotics in the prevention of undigested gliadin peptides toxic effects.
    International Journal of Food Sciences and Nutrition 07/2014; · 1.20 Impact Factor
  • Riccardo Troncone, Valentina Discepolo
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    ABSTRACT: Celiac disease (CD) has a multifactorial etiology with complex genetics and frequently occurs in association with other autoimmune disorders. Even though triggered by a dietary antigen, it shows many autoimmune features, the most peculiar being the presence of high titers of anti-tissue transglutaminase 2 autoantibodies, produced in the small intestinal mucosa since the early stages of the disease. More than 60% of CD-associated susceptibility loci are shared with at least another autoimmune condition, suggesting common pathogenic mechanisms. In particular, recognition of peptides by HLA molecules, posttranslational modifications required for optimal peptide binding and immune mechanisms leading to tissue damage have been found in CD as well as in other autoimmune diseases. This review briefly summarizes the main autoimmune features of CD, underlining the similarities with other autoimmune disorders, in particular with type 1 diabetes mellitus. Furthermore, the role of gluten and microbiome in driving autoimmunity is discussed.
    Journal of Pediatric Gastroenterology and Nutrition 07/2014; 59 Suppl 1:S9-S11. · 2.87 Impact Factor
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    ABSTRACT: The requirements for and conditions of subspecialty training in Paediatric Gastroenterology, Hepatology and Nutrition (PGHN) are rather variable across European countries. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) agreed on a training syllabus aimed to foster a harmonized European PGHN curriculum, and to support national PGHN societies and governmental bodies to promote and establish high quality training programmes and levels of certification in the field. The document provides PGHN training prerequisites and objectives and the basic knowledge elements to acquire the clinical, technical and management skills needed. Guidelines and instruments for self-monitoring and appraisal are proposed, and a logbook is available online. These training standards are a first step towards a European certification and recognition as a specialist in PGHN.
    Journal of pediatric gastroenterology and nutrition. 06/2014;
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    ABSTRACT: Background and aims Little evidence demonstrating the correlation between several single nucleotide polymorphisms and a specific phenotype of Crohn's disease has been reported in children. We investigated the relationship between autophagy genes variants and clinical features in our children with Crohn's disease. Methods Genotyping for ATG16L1, NOD2/CARD15, and IRGM1 was performed in 80 consecutive patients with Crohn's disease (median age: 11 years; range: 0.7–17.9 years). Crohn's disease location and behaviour were classified using the Paris classification. Additional data were collected from clinical records on patients’ demographics, age at symptom onset and diagnosis, extraintestinal manifestations, therapy, clinical relapses, and need of surgical intervention. Results Patients homozygous for the risk allele ATG16L1 (T300A) showed a trend towards switching to a stricturing phenotype during the course of disease compared to children either homozygous for the wild-type allele or heterozygous for the ATG16L1 single nucleotide polymorphism (p = 0.01). Homozygosity for the ATG16L1 risk allele was associated with a major recurrence of clinical relapses and earlier introduction of immunosuppressants (p = 0.006 and p = 0.04, respectively). Heterozygosity for the NOD2 rs2066847 allele was associated with major ileal involvement (p = 0.01). Conclusion In patients carrying the T300A variant, Crohn's disease follows a more aggressive clinical course.
    Digestive and Liver Disease 06/2014; · 2.89 Impact Factor
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    ABSTRACT: Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease.
    BMC Medicine 05/2014; 12(1):85. · 7.28 Impact Factor
  • Journal of pediatric gastroenterology and nutrition. 05/2014;
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    ABSTRACT: Children comprise one fifth of Europe's population. Promoting child health and development is of key importance for society and it's future. This position paper highlights opportunities of investing in gastrointestinal, liver and nutritional research to promote child health and delineates priorities for research. Investing in child health plays a key role for promotion of population health, well-being, and disease prevention life long, with large health economic benefits. Major opportunities for improving knowledge and translational application arise from recent scientific and technological developments, e.g. the long term impact of early environmental cues interacting with genes. Personalised approaches to therapy and prevention should be enhanced. Deciphering the microbiome and its effects on functions can help promoting long-term health. Epigenetic research can help to understand how early environmental factors influence later gastrointestinal and hepatic health and disease. A linked nutrition and physical activity strategy can promote health and prevent nutritional deficiencies, inactivity and chronic non-communicable diseases such as diabetes, to ensure optimal health and cognition. Special attention should be devotes to populations with low socio-economic status, migrant background and ethnic minorities, and to critical life periods including pregnancy, lactation, infancy and childhood. Improved understanding on optimal nutrition and on maintaining gut and liver homeostasis throughout childhood will help prevent chronic diseases in later life.
    Journal of pediatric gastroenterology and nutrition 05/2014; · 2.18 Impact Factor
  • Gastroenterology 05/2014; 8:S397–S398. · 13.93 Impact Factor
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    ABSTRACT: OBJECTIVES:Potential celiac disease (CD) is defined by the presence of serum anti-tissue-transglutaminase (anti-TG2) antibodies and normal duodenal mucosa. The major clinical problem is the management of asymptomatic patients and how to predict the development of villous atrophy. This prospective longitudinal cohort study describes the natural history of potential CD up to 9 years and explores risk factors associated with the development of mucosal damage.METHODS:Two hundred and ten potential CD children were eligible for the study; 175/210 asymptomatic children were left on a gluten-containing diet. Antibodies and clinical symptoms were checked every 6 months, and a small bowel biopsy was taken every 2 years to evaluate histological, immunohistochemical, and anti-TG2 deposits. Patients were genotyped for HLA and a set of non-HLA CD-associated genes.RESULTS:Forty-three percent of patients showed persistently elevated anti-TG2 level, 20% became negative during follow-up, and 37% showed a fluctuant anti-TG2 course with transiently negative values. At 3 years of follow-up, 86% of cases remained potential; 73 and 67% still had normal duodenal architecture at 6 and 9 years, respectively. Male sex, slight mucosal inflammation at time 0, and a peculiar genetic profile delineate a cohort of individuals who were prone to develop mucosal damage during time.CONCLUSIONS:A sizeable proportion of asymptomatic potential celiac patients showed fluctuation or negativization of antibody production, and many of these, with persistently positive anti-TG2, did not develop mucosal damage after 9 years of follow-up. Celiac population is a multivariate aggregate of individuals with different genetic and phenotypic profiles. Caution is required before prescribing a gluten-free diet for life to asymptomatic individuals with potential CD.Am J Gastroenterol advance online publication, 29 April 2014; doi:10.1038/ajg.2014.77.
    The American Journal of Gastroenterology 04/2014; · 9.21 Impact Factor
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    ABSTRACT: It is always known that anti-tissue transglutaminase2 (anti-TG2) antibodies are produced in the small intestine. Their serum titers correlate with mucosal damage degree and decrease on gluten-free-diet (GFD). We aimed to correlate intestinal anti-TG2 antibodies levels with degree of mucosal damage and the GFD duration. Thirty-four active, 71 potential and 24 CD patients on GFD for at least 2 years, were enrolled. Anti-TG2 deposits were detected in intestinal biopsies by double immunofluorescence. Biopsies were cultured for 24h with medium, and with gliadin peptic tryptic digest (PTG) or A-gliadin peptide 31-43 (P31-43). Anti-TG2 antibodies secreted into supernatants were measured by ELISA. All active CD patients secreted into culture medium high titers of anti-TG2 antibodies that increased with the worsening of mucosal injury (Spearman r=0.71; p<0.0001). 70/71 potential CD patients and 15/24 treated CD patients secreted low titers of anti-TG2 antibodies into supernatants, 8/9 negative treated patients being on GFD for more than 10 years. An inverse correlation between antibody titers and duration of GFD was found (Spearman r= -0.52; p<0.01). All active, 53/71 potential and 6/24 treated CD patients showed anti-TG2 mucosal deposits. 5/6 positive treated CD patients had been on GFD for less than 6 years and were also positive for secreted anti-TG2. In treated patients PTG/P31-43 was not able to induce secretion of anti-TG2 antibodies into culture medium. Measurement of anti-TG2 antibodies in biopsy supernatants proves to be more sensitive than detection by immunofluorescence to reveal their intestinal production. Intestinal antiTG2 antibodies titers positively correlate with the degree of mucosal damage and inversely with the duration of GFD.
    Clinical & Experimental Immunology 04/2014; · 3.28 Impact Factor
  • Riccardo Troncone, Raanan Shamir
    Journal of pediatric gastroenterology and nutrition 03/2014; · 2.18 Impact Factor
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    ABSTRACT: This position statement summarises a view of academia regarding standards for clinical research in collaboration with commercial enterprises, focussing on trials in pregnant women, breastfeeding women and children. It is based on a review of the available literature and an expert workshop co-sponsored by the Early Nutrition Academy and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Clinical research collaborations between academic investigators and commercial enterprises are encouraged by universities, public funding agencies and governmental organisations. One reason is a pressing need to obtain evidence on the effects, safety and benefits of drugs and other commercial products and services. However, the credibility and value of results obtained through public private research collaborations have been questioned, since many examples of inappropriate research practice have become known. Clinical research in pregnant and breastfeeding women, and in infants and children, raise sensitive scientific, ethical and societal questions and require the application of particularly high standards. Here we provide recommendations for the conduct of public private research collaborations in these populations. In the interest of all stakeholders these recommendations should contribute to more reliable, credible and acceptable results of commercially sponsored trials and to reducing the existing credibility gap.
    Journal of pediatric gastroenterology and nutrition 01/2014; · 2.18 Impact Factor
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    Digestive and Liver Disease 01/2014; 4(Suppl 1 3rd Pediatric Allergy and Asthma Meeting (PAAM)Publi):P20. · 2.89 Impact Factor
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    ABSTRACT: Congenital chloride diarrhea (CLD) is an autosomal recessive disorder characterized by life-long, severe diarrhea with intestinal Cl- malabsorption. It results from a reduced activity of the down regulated in adenoma exchanger (DRA), due to mutations in the solute carrier family 26, member 3 (SLC26A3) gene. Currently available therapies are not able to limit the severity of diarrhea in CLD. Conflicting results have been reported on the therapeutic efficacy of oral butyrate. We investigated the effect of oral butyrate (100 mg/kg/day) in seven CLD children with different SLC26A3 genotypes. Nasal epithelial cells were obtained to assess the effect of butyrate on the expression of the two main Cl- transporters: DRA and putative anion transporter-1 (PAT-1). A variable clinical response to butyrate was observed regarding the stool pattern and fecal ion loss. The best response was observed in subjects with missense and deletion mutations. Variable response to butyrate was also observed on SLC26A3 (DRA) and SLC26A6 (PAT1) gene expression in nasal epithelial cells of CLD patients. We demonstrate a genotype-dependency for butyrate therapeutic efficacy in CLD. The effect of butyrate is related in part on a different modulation of the expression of the two main apical membrane Cl- exchangers of epithelial cells, members of the SLC26 anion family.Trial registration: Australian New Zealand Clinical trial Registry ACTRN12613000450718.
    Orphanet Journal of Rare Diseases 12/2013; 8(1):194. · 3.96 Impact Factor
    This article is viewable in ResearchGate's enriched format
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    ABSTRACT: Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Undigested gliadin peptides P31-43 and P57-68 induce innate and adaptive T cell-mediated immune responses, respectively. Alterations in the cell shape and actin cytoskeleton are present in celiac enterocytes, and gliadin peptides induce actin rearrangements in both the CD mucosa and cell lines. Cell shape is maintained by the actin cytoskeleton and focal adhesions, sites of membrane attachment to the extracellular matrix. The locus of the human Lipoma Preferred Partner (LPP) gene was identified as strongly associated with CD using genome-wide association studies (GWAS). The LPP protein plays an important role in focal adhesion architecture and acts as a transcription factor in the nucleus. In this study, we examined the hypothesis that a constitutive alteration of the cell shape and the cytoskeleton, involving LPP, occurs in a cell compartment far from the main inflammation site in CD fibroblasts from skin explants. We analyzed the cell shape, actin organization, focal adhesion number, focal adhesion proteins, LPP sub-cellular distribution and adhesion to fibronectin of fibroblasts obtained from CD patients on a Gluten-Free Diet (GFD) and controls, without and with treatment with A-gliadin peptide P31-43. We observed a "CD cellular phenotype" in these fibroblasts, characterized by an altered cell shape and actin organization, increased number of focal adhesions, and altered intracellular LPP protein distribution. The treatment of controls fibroblasts with gliadin peptide P31-43 mimics the CD cellular phenotype regarding the cell shape, adhesion capacity, focal adhesion number and LPP sub-cellular distribution, suggesting a close association between these alterations and CD pathogenesis.
    PLoS ONE 11/2013; 8(11):e79763. · 3.53 Impact Factor
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    ABSTRACT: Celiac disease (CD) occurs frequently, and is caused by ingestion of prolamins from cereals in subjects with a genetic predisposition. The small intestinal damage depends on an intestinal stress/innate immune response to certain gliadin peptides (e.g., A-gliadin P31-43) in association with an adaptive immune response to other gliadin peptides (e.g., A-gliadin P57-68). Gliadin and peptide P31-43 affect epithelial growth factor receptor (EGFR) signaling and CD enterocyte proliferation. The reason why the stress/innate immune and proliferative responses to certain gliadin peptides are present in CD and not in control intestine is so far unknown. The aim of this work is to investigate if, in CD, a constitutive alteration of enterocyte proliferation and signaling exists that may represent a predisposing condition to the damaging effects of gliadin. Immunofluorescence and immunohistochemistry were used to study signaling in CD fibroblasts and intestinal biopsies. Western blot (WB) analysis, immunoprecipitation, and quantitative PCR were also used. We found in CD enterocytes enhancement of both proliferation and Epidermal Growth Factor Receptor (EGFR)/ligand system. In CD enterocytes and fibroblasts we found increase of the phosphorylated downstream signaling molecule Extracellular Signal Regulated Kinase (ERK); block of the ERK activation normalizes enterocytes proliferation in CD mucosa. In conclusion the same pathway, which gliadin and gliadin peptide P31-43 can interfere with, is constitutively altered in CD cells. This observation potentially explains the specificity of the damaging effects of certain gliadin peptides on CD intestine.
    PLoS ONE 10/2013; 8(10):e76006. · 3.53 Impact Factor

Publication Stats

5k Citations
1,473.75 Total Impact Points


  • 2013–2014
    • University of Chicago
      Chicago, Illinois, United States
  • 1994–2014
    • University of Naples Federico II
      • • Department of Translational Medical Sciences
      • • Department of Molecular Medicine and Health Biotechnology
      Napoli, Campania, Italy
  • 1984–2013
    • Second University of Naples
      Caserta, Campania, Italy
  • 2011
    • Royal Free London NHS Foundation Trust
      Londinium, England, United Kingdom
  • 1999–2011
    • National Research Council
      • • Institute of Food Sciences ISA
      • • Institute of Endocrinology and Experimental Oncology IEOS
      Roma, Latium, Italy
    • Université de Versailles Saint-Quentin
      Versailles, Île-de-France, France
  • 2002–2010
    • Università degli Studi di Salerno
      • Department of Chemistry and Biology DCB
      Salerno, Campania, Italy
    • American Society for Nutrition
      American Fork, Utah, United States
  • 2008
    • Academisch Medisch Centrum Universiteit van Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2006
    • Hadassah Medical Center
      • Department of Paediatrics
      Yerushalayim, Jerusalem District, Israel
  • 2003–2005
    • Università degli Studi di Trieste
      • Department of Life Sciences
      Trieste, Friuli Venezia Giulia, Italy
  • 1998
    • Shaare Zedek Medical Center
      • Department of Pediatrics
      Jerusalem, Jerusalem District, Israel
  • 1991
    • The University of Edinburgh
      • Gastro-Intestinal Unit
      Edinburgh, SCT, United Kingdom
  • 1988
    • Western General Hospital
      Edinburgh, Scotland, United Kingdom