[Show abstract][Hide abstract] ABSTRACT: Background
Basophils are important effectors cells in allergic rhinitis (AR) since they are involved in immunoglobulin (Ig) E – mediated inflammation and in the release of pro-inflammatory mediators. Specific subcutaneous immunotherapy (SCIT) provides clear immunologic modulation in some immune cells, however its systemic effects on basophils are not well known.
Peripheral blood (PB) samples from 43 patients with allergic rhinitis mono-sensitized to Dermatophagoides pteronyssinus (Dpt) [33 of them under SCIT with allergoid Dpt extract, in maintenance dose (SCIT), with evaluation just before SCIT injection (SCIT-T0) and 4 hours later (SCIT-T4) and the other 10 Dpt allergic patients never having, in the past, undergone specific immunotherapy treatment (NSIT)], and 15 healthy age- and gender-matched controls (HG), were analyzed. For each sample, the total (t-IgE) and specific IgE (s-IgE) was performed, as well as, the relative frequency and absolute number of PB basophils and receptor-bound IgE and IgG expression were evaluated by flow cytometry and the Histamine N-methyltransferase (HNMT) and tryptase α/β1 (TPSAB1) gene expression was assessed by real-time PCR.
Higher levels of receptor-bound IgE were observed in SCIT patients, which are correlated with the levels of serum t-IgE and s-IgE, whereas no significant differences were observed for receptor-bound IgG. Regarding HNMT mRNA expression, significantly lower expression levels were detected in AR patients compared to HG, independently of type of therapy. Moreover a negative correlation was found between HNMT gene expression and time under SCIT. Conversely, tryptase gene expression was significantly up-regulated in NSIT when compared to HG; however in SCIT patients, tryptase gene expression was significantly decreased than in NSIT patients. No differences were found for any parameter between SCIT-T0 and SCIT-T4 with exception of a transient increased expression of tryptase in SCIT-T4.
PB basophils from patients with AR show altered functional features, which seems to be influenced by SCIT, suggesting that these cells could be useful to clarify the SCIT triggered mechanisms at a systemic level.
Allergy Asthma and Clinical Immunology 10/2013; 9(1).
[Show abstract][Hide abstract] ABSTRACT: T cell receptor excision circles (TREC) on CD31+ T cells are related to recent thymic emigrant cells (RTEs). The involvement of the functional thymic tissue occurs early in the IgE-mediated allergic reaction, and in response to specific immunotherapy (SIT).
Evaluation of specific immunotherapy effects on TREC number in peripheral T cells in patients allergic to Dermatophagoides pteronyssinus (Dpt).
85 respiratory allergic patients (both genders), 41 of them (Group II) under maintenance treatment to Dpt SIT (21 sublingual-SLIT, and 20 subcutaneous-SCIT), were selected. The allergic patients (Group I) without specific treatment were submitted to an allergen challenge test (22 nasal and 22 conjunctival). Peripheral cell analysis was performed immediately before treatment and 60 or 240 minutes after allergenic extract administration. TREC quantification was performed in CD4+CD31+ and CD8+CD31+. The results were expressed per 100.000 cells related to RTEs. Samples from 10 healthy individuals (Control - Group III) were obtained with the same method.
The value of TRECs on RTEs was constant in control groups. For Group I patients (nasal or conjunctival test), TREC quantification in CD31+ T cells showed relevant individual changes, even in the patients tested earlier (60 minutes), and statistical significant at 240 minutes. Both SCIT and SLIT had also demonstrated enormous individual changes, particularly on TRECs/CD4+CD31+ cells assay. Basal values in Group III were significantly higher than those observed in active patients groups.
Thymic functional activity is earlier involved in the allergic reaction and SIT IgE-mediated allergy is able to induce RTEs in the periphery, particularly TRECs/CD4+CD31+ cells. Both SLIT and SCIT showed reduced RETs in the periphery, probably due to maturation of regulatory T cells. Our results suggest a crucial role of the functional thymic tissue on the central mechanism of this therapy.
European annals of allergy and clinical immunology 04/2012; 44(2):61-72.
[Show abstract][Hide abstract] ABSTRACT: Inhaled combined therapy improves the pulmonary function in asthmatic patients. The effect on the airway hyperresponsiveness (AHR) and the efficacy of different pharmacological schedules is not well clarified on adolescent asthmatics.
Evaluate the responses to different combined inhaled therapies in adolescent asthmatics and study its impact on exercise induced AHR.
Basal lung function tests (LFT) were performed in 30 adolescents (13 to 16 years old; 19 female) with allergic asthma. They were submitted to exercise challenge test (EC) followed by bronchodilator test (BD). During 4 weeks, 15 adolescents were submitted to inhaled fluticasone/salmeterol (group A) and other 15 to inhaled budesonide/formoterol (group B). After this period, they underwent another functional evaluation as previous.
Before treatment, pulmonary function was similar in both groups. After 4 weeks of treatment, these groups showed an improvement of the basal LFT (p = 0.001 for FEV1 in both), decrease on bronchoconstriction induced by exercise (NS for both) and less recovery on BD response (p = 0.001 and 0.002, for FEV1 respectively groups A and B). Group B showed a better performance, with higher improvement of basal FEF 25/75 (p = 0.001), reduced bronchoconstriction response to EC (p = 0.008 for FEV1) and fewer response to BD test (p < 0.0001 for FEV1 and 0.024 for FEF 25/75) No adverse events were observed.
After 4 weeks of inhaled combined therapy, these patients improved their pulmonary function and bronchomotricity. Those under budesonide/formoterol showed the highest improvement. These medications are a safe measure in controlling the asthma in these patients.
European annals of allergy and clinical immunology 02/2012; 44(1):12-7.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The primary role of infections in chronic urticaria (CU) is controversial. We hypothesised that streptococcal tonsillitis (ST) could be a primary cause of CU or acute recurrent urticaria (ARU). METHODS: Retrospective study of 14 outpatients observed between January 2000 and December 2009, with CU/ARU and clinical and/or laboratorial suspicion of an aetiopathogenic link with ST. Clinical history, objective examination and laboratorial study were looked for. Three groups were defined: spontaneous resolution of urticaria, resolution after tonsillectomy, and still symptomatic. RESULTS: In these patients, a causal relationship between ST and urticaria is supported by: markers of streptococcal infection, the perception of a clinical relationship between tonsillitis and urticaria, the decrease of urticaria severity with early antibiotherapy to tonsillitis and urticaria resolution after tonsillectomy. CONCLUSIONS: Our study encourages the investigation of tonsillitis in these otherwise idiopathic patients, especially until young adulthood and even in the absence of any symptoms.
Allergologia et Immunopathologia 10/2011; · 1.23 Impact Factor
Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 01/2011; 21(2):154. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: High-resolution computed tomography (HRCT) is a widespread medical imaging method for the study of thoracic diseases. In asthma it is very useful particularly when it is difficult to achieve an effective control of disease, and in severe deterioration.
It was intended to evaluate the imaging changes by HRCT in asthmatic patients and to assess the expression according to the symptoms and duration of disease.
Thirty three patients from the Outpatient Department, with asthma classified in the different clinical severity stages according to GINA, were randomly included. They were submitted to HRCT (Somaton Plus-4, Siemens). The lesions were classified in reversible (mucoid impaction, acinar pattern centrilobular nodules and lobar collapse) and irreversible (bronchiectasis, bronchial wall-thickening, sequellar line shadows and emphysema).
The 33 asthmatic patients (20 female) had an average age of 44.76 +/- 16.98 years and a mean disease evolution time of 23.39 +/-14.83 years. 30% had mild persistent asthma, 43% moderate persistent asthma and 27% severe persistent asthma. All the patients were under inhaled corticotherapy. Only 6 patients had normal HRCT 4 with mild persistent asthma (4 to 25 years of duration of disease) and 2 with moderate persistent (10 to 48 years of duration of disease). 81.81% of the patients had changes in HRCT, being the irreversible lesions the most frequent. The most important irreversible lesions were observed in severe asthma patients with longer duration of disease. All the patients with reversible lesions had also irreversible changes. Most of the bronchiectasis were centrally located and were found in severe asthma patients. Irreversible changes were identified in 3 patients with mild asthma and a maximum of 6 years of duration of disease.
HRCT findings were related with asthma severity and long lasting disease but there are some asthmatics that also present early abnormalities, even in milder forms. All the groups of asthmatic patients presented all types of imaging changes, including the irreversible ones. In asthma these changes can be the result of individual patterns of response to frequent exacerbations, leading to a persistent chronic inflammatory process that will determine airway remodelling, even in early stages of disease and/or mild asthma.
European annals of allergy and clinical immunology 10/2009; 41(5):139-45.
Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 02/2009; 19(3):242-4. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: CD86 is a well-known costimulatory molecule in its interaction with CD28 and/or CTLA present on T cells, and is essential for full activation of naïve T-cell and subsequent differentiation. Usually the B7 molecules are expressed mainly on APCs and B cells and in specific conditions on other activated cells. These costimulatory molecules are involved in the development of allergic inflammation and airways hyperreactivity (AHR) in allergen-challenged mice. Activated T cells, CD4(+)CD25(+), express CD86 in the first 60 minutes after the specific inhalatory exposure. These T cells can be relevant in IgE mediated allergic reaction possibly by an autocrine costimulation via CD28/CTLA activation pathway. The blockage of the expression of CD86 could be a potential therapeutical target to reduce the magnitude or the progression of the allergic reaction. The review article also discussed relevant patents.
Recent Patents on Inflammation & Allergy Drug Discovery 02/2009; 3(2):128-31.
[Show abstract][Hide abstract] ABSTRACT: Food allergy is an increasing problem with limited therapeutic approaches apart from to the eviction diet.
A 40-year-old female patient with food allergy symptoms was polysensitized to almost all vegetable food since the age of 36; the onset of symptoms was during pregnancy. The allergological study demonstrated positive skin prick tests (SPT) to nuts, legumes, cereals, spices, several fresh fruits including peach, and other groups of vegetable foods however, it was negative to common aeroallergens. Serum specific IgE levels were negative (<0.35 kU/L) to profilin and carbohydrate determinants, but positive to Pru p 3 (3.5 kU/L). Positive double-blind placebo-controlled food challenge to peach confirmed the allergic disease. She received specific sublingual immunotherapy with native Pru p 3 at a concentration of 40 mug/ml with 5 administrations per week and a cumulative dose of 200 mug of nPru p 3 per month. After an ultra-rush build-up phase concluded in one day she continued therapy during a year with 5 administrations per week. The clinical evolution and laboratory studies demonstrated an early reduction on SPT reactions with no relevant changes on serum specific IgE, IgG, IgG(1) and IgG(4) to Pru p 3 during the immunotherapy period. The challenge test was negative 4 months after the beginning of the SLIT. Regarding clinical response she markedly improved after the first month of treatment, and by the 3th month she had no major vegetable dietary restrictions, except for nuts and pepper.
These results demonstrate the excellent efficacy and safety of sublingual specific protein immunotherapy developed according to the patient specific sensitivity profile to Pru p3.
[Show abstract][Hide abstract] ABSTRACT: We report the case of a 21-year old man with a long-standing history of severe asthma and allergic rhinosinusitis who developed progressive worsening of dyspnea, wheezing, productive cough, and nasal obstruction, with little response to antibiotics and repeated short courses of oral corticosteroids. A diagnosis of allergic bronchopulmonary aspergillosis was made on the basis of a combination of clinical, laboratory and radiographic findings.Treatment with oral methylprednisolone and itraconazole resulted in an improvement in symptoms, lung function and computed tomography results, as well as in a decrease in total serum immunoglobulin E. This case report highlights the importance of a high degree of clinical suspicion in order to diagnose and treat allergic bronchopulmonary aspergillosis in patients with a long-standing history of severe asthma as early as possible as this has a major impact on prognosis. It also highlights the effectiveness of itraconazole as adjunctive therapy to systemic corticosteroids in this condition.
Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 01/2009; 19(5):404-8. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Overweight and obesity are major health issues in Western societies. They are related with a higher risk of different co-morbidities but their relationship with airway hyperresponsiveness (AHR) is still under discussion. Nevertheless, they are related to higher severity in asthma and other respiratory diseases. The aim of the study was to analyze the AHR in individuals with normal lung function without respiratory disorders, according to body mass index (BMI) calculation.
We performed clinical observation and basal lung function tests (LFT) in 595 consecutive individuals in order to exclude respiratory disease. 377 individuals fulfilled the criteria of normal values according international guidelines. They were submitted to standardized treadmill exercise test followed by bronchodilator test. FVC, FEV1, FEF 25/75, RV and Raw were obtained at different conditions according to BMI groups (I: lean; II: normal; III: overweight; IV obese).
55.2% of the sample was overweight or obese, and a signficant relationship was found with female gender and older ages (p=0.0046 and p<0.0001 respectively). The positive response to exercise test or bronchodilator beta2 agonists was not significantly frequent compared with the other groups. In obese individuals the exercise markedly reduced basal Raw and increased FEF 25/75. Lean individuals showed higher basal values of RV that was reduced upon exercise. Response to 12 agonists showed no differences according to weight biotypes.
BMI hampers lung function in normal individuals, and seems not to be related to AHR. Regular exercise should be encouraged in overweight and obese individuals, since it increases their bronchial permeability as shown in lower frequency of positive exercise tests. The same is advisable for lean individuals for different reasons. Their increased basal RV and Raw improve upon exercise. Despite overweight and obesity are being related to a low-grade of basal systemic inflammation, there was no association with a higher basal bronchial hyperresponsiveness in these individuals.
European annals of allergy and clinical immunology 01/2009; 40(4):130-7.
[Show abstract][Hide abstract] ABSTRACT: Profilin is a panallergen found in pollens and fruits. Sensitization to this protein may explain some sensitization to multiple pollen species. We aimed to evaluate sensitization to profilin in patients suffering from respiratory allergy sensitized to pollens, in the Central region of Portugal.
Patients were evaluated for asthma symptoms, rhinitis, conjunctivitis and food allergy. Skin prick tests (SPT) to aeroallergens including 12 different pollens and profilin (nPho d 2) were performed. The patients were divided into two study groups according to the region of residence: A--inland region and B--coastal region.
A total of 370 patients were evaluated (277-group A; 93-group B). 65.9% showed positive skin prick tests and 76.2% were positive to pollens (87.1%-group A; 42.85%-group B; p<0.0001). All the patients sensitized to pollens had rhinitis (p=0.001). Sensitization to profilin was associated with pollen sensitization (p=0.014). 43 patients were sensitized to profilin (40-group A; 3-group B; p=0.006). 21.0% of patients sensitized to pollens, were also sensitized to profilin. 39 patients were sensitized to at least two pollens (p<0.0001). Four profilin and pollen sensitized patients had oral allergy syndrome complaints to melon. This syndrome was related with profilin sensitization (p=0.001).
It is advisable to perform SPT to profilin, particularly in the Inland region, for a better differential diagnosis between cross-reactivity and true sensitization to pollens. The results together with the medical history may support the choice for a specific immunotherapy option.
Science of The Total Environment 10/2008; 407(1):273-8. · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An autoimmune pathogenic mechanism is implicated in about one-third of patients with chronic urticaria (CU), involving circulating functional autoantibodies to either the high affinity IgE receptor (LgG1/IgG3 anti-FcARI) or to IgE, with histamine releasing activity. New therapeutic approaches had been developed for patients with severe or unresponsive to treatment symptoms, including the use of intravenous immunoglobulins (IVIG) as immunomodulators.
To assess the efficacy of IVIG treatment in patients with evidence of autoimmune CU.
A group of 29 patients (F = 20, M = 9) with the diagnosis of autoimmune CU were selected from the outpatient department. All the patients showed daily symptoms of urticaria and/or angioedema, with unsatisfactory response to conventional therapy and a positive intradermal autologous serum test (AST). They were submitted to low dose of IVIG treatment each 4 weeks (0.15 g/kg), for a minimum of 6 months and a maximum of 51 months. They were evaluated for clinical scores, need of oral medication and AST results, before and after treatment.
A clinical improvement was observed in 26 patients, with reduction of urticaria or angioedema complaints (p < 0.0001) and decreasing need for oral antihistamine medication (p = 0.002). 3 patients drop-out the treatment: one depending of severe adverse event and the other 2 with no response after the 5th treatment. 19:26 patients achieved complete remission of symptoms. A reduction of histamine-releasing activity was found in the majority of the patients, documented by the decrea, se of reactivity in AST at the end of the treatment (p = 0.002). 20 patients remained without symptoms during 12 months after. the active treatment, and the other 6 only reported non-severe complaints.
IVIG is an effective therapeutic option in patients suffering from severe CU refractory to conventional treatment, in which autoimmune mechanism is involved. The efficacy persists for at least 12 months after treatment. However, the number of infusions needed to achieve clinical control, showed great range between patients.
European annals of allergy and clinical immunology 10/2007; 39(7):237-42.
[Show abstract][Hide abstract] ABSTRACT: There are several immunological and clinical effects induced by specific immunotherapy (SIT). A reduction of reactivity to allergen is the final propose of this therapy. The aim of this study was to evaluate the specific cutaneous reactivity, two years after beginning SIT.
We included 95 patients with bronchial asthma (BA) and/or allergic rhinitis (AR) to house dust mites (HDM). 74 patients were submitted to subcutaneous SIT with commercial extracts of Dermatophagoides. The control group included the 21 patients without SIT. After a two years period, the cutaneous reactivity was reassessed, by skin prick tests (SPT). The effect of SIT in the cutaneous response was evaluated by calculating the difference between the wheal diameter of the SPT before and after treatment. A positive difference indicated a cutaneous reactivity reduction.
The patients submitted to SIT included 52.7% males and 47.3% females, with a mean age of 18.4 +/- 13.9 years old. The cutaneous reactivity to D. pteronyssinus, before and two years after the beginning of SIT, were 6.9 +/- 3 mm and 5.1 +/- 2.9 mm, respectively, with 1.87 of difference (p = 0.0001). The cutaneous reactivity to D. farinae, before and two years after the beginning of SIT, were 6.2 +/- 2.4 mm and 5.0 +/- 3.7 mm, respectively, with 0.93 of difference (p = 0.0790). In the control group, the cutaneous reactivity to D. pteronyssinus was 4.4 +/- 2.1 mm and two years later it was 8.2 +/- 3.7 mm. The difference was -1.53 (p = 0.1590). The cutaneous reactivity to D. farinae was 4.6 +/- 2.2 mm in the first evaluation and 8.3 +/- 4.7 mm two years later. The difference was -2.63 (p = 0.0470).
This study showed a significant reduction of specific cutaneous reactivity induced by Dermatophagoides SIT. In the control group the cutaneous reactivity to Dermatophagoides revealed an increment.
European annals of allergy and clinical immunology 02/2007; 39(1):5-8.
[Show abstract][Hide abstract] ABSTRACT: Goat's milk (GM) allergy not associated with allergy to cow's milk (CM) is a rare disorder. Caseins have been implicated has the major allergens eliciting symptoms.
We report the case of a 27 years-old female patient that experienced two episodes of urticaria related to ingestion of goat's cheese (GC). She tolerated CM, dairy products and sheep cheese. Skin prick tests were performed with GM, CM, bovine casein and alpha -lactalbumin and fresh milk and GC. Serum specific IgE to GM, CM and its fractions, and GM and CM immunobloting assays with inhibition were also evaluated.
Skin tests were positive to GM and GC and negative to CM. GM immunoblot showed an IgE-binding 14 kDa band that was totally inhibited after serum pre-incubation with GM.
Allergens other than casein can be involved in allergy to GM. Even small quantities of protein can elicit symptoms.
Allergologia et Immunopathologia 01/2007; 35(3):113-6. · 1.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Occupational allergy among florists and people who work in cut flower production of Alstroemeria cultivars (Peruvian lily or Inca lily) has been previously reported. The allergen involved in sensitization is tulipalin A (alpha-methylene-gamma-butyrolactone).
We describe the case of a 65-year-old woman who developed severe dermatitis on her right thumb, index and middle fingers and less severe dermatitis on her left palm and front of forearm with occasional itching of the neck and face after taking up home gardening activities, including cutting flowers such as Alstroemeria.
The patient and three healthy individuals were submitted to epicutaneous tests with the European standard series, the plant series, and stem portions of three suspected ornamental plants (Alstroemeria, Lilium and Zantedeschia), garlic, and onion.
Patch tests performed in our patient, revealed an extreme reaction (+ + +) to Alstroemeria and alpha-methylene-gamma-butyrolactone, a strong reaction (+ +) to propolis and wood tar mix, a weak reaction (+) to balsam of Peru, an irritant reaction to garlic and negative results to diallyl disulfide and the other components investigated. Patch tests performed in the healthy individuals revealed negative.
We stress the importance of Alstroemeria as a cause of allergic contact dermatitis not only in workers involved in the flower trade, but also in other people that come into contact with this plant in their leisure activities.
Allergologia et Immunopathologia 01/2006; 34(2):73-5. · 1.23 Impact Factor