Increased IL-21 Expression Induces Granzyme B in Peripheral CD5(+) B Cells as a Potential Counter-Regulatory Effect in Primary Sjögren's Syndrome.

Recently, we reported elevated proportions of circulating follicular T helper cells and higher levels of interleukin- (IL-) 21 in primary Sjögren's syndrome (pSS). Interaction of invariant natural killer T (iNKT) cells with B cells and granzyme B (GrB) production may be also important in pSS. Thirty-two pSS patients and 24 healthy controls were enrolled in our study. We investigated the expression of intracellular GrB and IL-21 receptor (IL-21R) of CD19(+)CD5(+) and CD19(+)CD5(-) B cells; furthermore, we determined the IL-21 expression of iNKT cells as well. We also assessed the proportion of transitional (CD19(+)CD24(high)CD38(high)), mature (CD19(+)CD24(int)CD38(int)) and primarily memory (CD19(+)CD24(high)CD38(-)) B cells. CD5(+) but not CD5(-) B cells showed elevated GrB and IL-21R expression in pSS; additionally IL-21 expression of iNKT cells was also elevated. The ratios of transitional and mature B cells were elevated in pSS, while primarily memory B cell percentages were decreased, which correlated with GrB and IL-21R expression of CD19(+) B cells. Our results suggest that enhanced IL-21R expression of CD19(+)CD5(+) B cells and production of IL-21 by iNKT cells may play an important role in the pathogenesis of pSS by regulating CD19(+)CD5(+) B cell functions and increasing GrB production, presumably leading to a counter-regulatory effect in the disease.

The assessment of immune-regulatory effects of extracorporeal photopheresis in systemic sclerosis: a long-term follow-up study.

The therapeutic options in systemic sclerosis (SSc) are limited mainly to the management of complications, and decelerating fibrosis and preventing disease progression are still great challenges. Extracorporeal photopheresis (ECP) is one of the promising therapeutic strategies in SSc; nevertheless, there is no consensus on the ideal timing and frequency of treatment cycles. In the present study, we evaluated the long-term effects of consecutive ECP treatments, and the stability of clinical and laboratory improvements. We enrolled nine patients with diffuse cutaneous SSc and performed 12 ECP cycles (24 ECP treatments) per patient in total. ECP cycles were carried out once in every 6 weeks, and each cycle consisted of two procedures. Sixteen healthy individuals served as controls for laboratory assessment. Following the sixth ECP cycle, we observed further improvement in skin score, which was confirmed by high-resolution ultrasonography as well. After the second ECP cycle, values of Tr1 and CD4+CD25(bright) Treg cells increased; however, Tr1 cells remained under control values until the 10th cycle. Suppressor activity of CD4+CD25+ Treg cells improved, while percentages of Th17 cells decreased. At the end of 12-month follow-up, we did not observe significant deterioration in skin involvement; however, improvement in laboratory parameters diminished after 12 months. If the first six ECP cycles are effective, uninterrupted continuation of treatment should be considered, which may lead to the normalization of Tr1 cell values along with further clinical improvement. Our laboratory observations indicate that immunomodulatory effect of ECP treatments lasts for 1 year only.

Investigation of Skin Barrier Functions and Allergic Sensitization in Patients with Hyper-IgE Syndrome.

PURPOSE: Hyper-IgE syndrome (HIES) is a severe primary immunodeficiency, characterized by increased serum IgE levels as well as recurrent infections and atopic dermatitis (AD)-like skin lesions. AD is a chronic inflammatory skin disease with immunologic alterations (Th2-Th22 polarization) and characteristic skin barrier dysfunctions. Our aim was to investigate physicochemical skin barrier alterations and allergic sensitization in STAT3-HIES patients in order to explore whether skin barrier dysfunction can play a role in the eczematoid skin lesions in these patients. METHODS: In our experiments STAT3 and FLG mutation analyses were performed in STAT3-HIES (n = 7) and AD (n = 49) patients. Laboratory parameters (LDH and Eos counts), immunologic alterations (Th17 cell counts), allergic sensitization (total and specific IgE levels, skin prick tests, and medical history records), skin barrier changes [transepidermal water loss (TEWL), skin pH], serum and stratum corneum thymic stromal lymphopoietin (TSLP) levels were also examined. RESULTS: Impaired Th17 cell numbers, but normal physicochemical barrier functions, as well as serum and stratum corneum TSLP levels, were found in STAT3-HIES, while these parameters were significantly altered in AD patients. Allergic sensitization was detected in nearly all AD patients, while no signs of sensitization occurred in STAT3-HIES. CONCLUSIONS: Our study demonstrated that the skin barrier functions of STAT3-HIES patients are not damaged and they differ significantly from the altered skin barrier functions of AD patients. A well-functioning physicochemical skin barrier may be one of the explanations on the contradiction between the extremely high total IgE levels and the lack of allergic sensitization in these patients. Our study underlines the importance of skin barrier in the development of allergic sensitization.

A novel large deletion and single nucleotide insertion in the Wiskott-Aldrich syndrome protein gene.

Deletion mutations of WAS are relatively rare and the precise localization of large deletions in the genome has rarely been described in previous studies. We report here a 5-month-old boy with a large deletion mutation in WAS that completely abolished protein expression. To localize the deletion, a 2816-bp-length sequence that spans between exons 9 and 12 was amplified. PCR amplification of the patient's sample revealed a single band of about 1 kb in contrast to the 2816-bp-amplicon in the control. Genomic DNA sequencing of the patient revealed a 1595-bp-deletion and an adenine insertion (g.5247_6841del1595insA). This large deletion of WAS resulted in partial loss of exon 10 and intron 11, and a complete loss of intron 10 and exon 11.

Regulatory T-cell subsets with acquired functional impairment: important indicators of disease severity in atopic dermatitis.

Our aim was to assess whether the presence of highly active effector T cells in atopic dermatitis (AD) is associated with changes in the number and/or function of regulatory T cells (Tregs). Flow cytometry was utilised to determine the percentage of CD4+ CD25bright CD127-/low FOXP3+ and skin-homing CLA+ CD4+ CD25bright FOXP3+ Tregs in healthy controls and AD patients. The correlation between disease severity and Treg percentages was estimated. Treg suppressor activity and cell proliferation were measured after T-cell stimulation. Significantly increased percentages of Tregs were found in AD patients compared to healthy individuals, and significant correlation between the frequency of Tregs and disease severity was also detected. The otherwise normal suppressor activity of Tregs decreased in the presence of Staphylococcus enterotoxin B (SEB). In conclusion, the continuous presence of SEB can trigger an acquired functional impairment of Tregs in AD patients and the correlation between the increased frequency of Tregs and disease severity supports their important role in AD pathogenesis.

The atopic skin-like microenvironment modulates the T-cell-polarising cytokine production of myeloid dendritic cells, as determined by laser scanning cytometry.

Because it is not known exactly when or where myeloid dendritic cells (mDCs) acquire their atopic dermatitis (AD)-specific T-cell-polarising ability in patients with this condition, we used laser scanning cytometry (LSC) to determine whether isolated peripheral blood mDCs from AD patients differed from cells from controls in their cytokine expression profiles de novo and after stimulation with Staphylococcus enterotoxin B (SEB) and thymic stromal lymphopoietin (TSLP), which represents an AD-like microenvironment. Unstimulated mDCs from AD patients showed pluripotent T-cell-polarising capacity, and the surrounding skin microenvironment was essential for the distinctive, disease-specific activity of mDCs (Th2-Th22 bias). We also emphasise that LSC is an attractive technique to study the effect of new DC-targeted therapeutic modalities in AD.

Changes in the number of CD8⁺ T lymphocytes in the peripheral blood of patients with various autoimmune diseases after autologous hematopoietic stem cell transplantations and their relations to the survival times.

The changes in the number of CD8⁺ T lymphocytes were studied before (0 day) and then 30 days after the autologous hematopoietic stem cell transplantations (AHSCT) in 14 therapy refractory patients with autoimmune diseases. The years of survival and the clinical states were also evaluated. The number of CD8⁺ T cells was determined by an hematologic automat and by flow cytometry. Longer than 5-year survival times were found in 6 cases, whereas there was no progression (improvement) in 2 cases, and 4 patients were lost. The increase in the number of CD8⁺ cytotoxic T cells was gradual in the first 2 months and reached the significantly highest values among all subtypes of lymphocytes. It was of a special interest that in all the 4 patients who died, the numbers of CD8⁺ T cells were less than 150/µl on the 30th day after AHSCT, whereas all the 10 patients with a higher cell number survived. These results suggest that the early monitoring of the number (not only the ratio) of regenerating CD8⁺ T cells in the peripheral blood can be a useful and quantitative laboratory measurement after AHSCT, and it has a significant relation also to the survival times of transplanted patients.

Follicular helper T cells may play an important role in the severity of primary Sjögren's syndrome.

The aim of this study was to investigate the possible role of follicular helper T (TFH) cells in the pathogenesis of primary Sjögren's syndrome (pSS) by analyzing immune-competent cells and serological markers with special emphasis on clinical symptoms. We enrolled 50 pSS patients and 16 healthy individuals in the study. Patients had elevated ratio of peripheral TFH cells, however, when dividing patients into two groups defined by the presence of extraglandular manifestations (EGMs), only patients with EGMs differed from controls significantly. Moreover, TFH cell percentages correlated positively with both activated T cell and Tr1 cell values. On the contrary, TFH cell percentages showed negative correlation with both IgM and IgG memory B cell proportions. Elevated TFH percent\ages were observed in the anti-SSA/SSB positive patients, and also in patients with higher IL-12, IL-21 levels and focus score values. Increased TFH cell proportions seem to have an important role in disease development.

Immunomodulatory effects of extracorporeal photochemotherapy in systemic sclerosis.

The aim of this study was to evaluate the clinical and immunomodulatory effects of extracorporeal photochemotherapy (ECP) in systemic sclerosis (SSc). We enrolled 16 patients with diffuse cutaneous SSc, who received 12 ECP treatments in total. After ECP treatments, the dermal thickness reduced and the mobility of joints improved. Internal organ involvement did not deteriorate. The percentages and numbers of peripheral Th17 cells decreased, the values of Tr1 and Treg cells increased, and the suppressor capacity of Treg cells improved. Interestingly, we found a positive correlation between the reduction of IL-17 levels and skin thickness measured by ultrasound. Moreover, levels of CCL2 and TGF-beta decreased, while the concentration of IL-1Ra, IL-10 and HGF elevated during the therapy. ECP treatments contribute to the restoration of disproportional autoimmune responses and attenuate fibrotic processes, thus decelerate the disease progression. Accordingly, ECP can be a useful element of novel treatment modalities proposed for SSc.

Altered peripheral invariant natural killer T cells in atopic dermatitis.

BACKGROUND: Conflicting data exist on the number of invariant NKT (iNKT) cells in atopic dermatitis (AD); furthermore, no data have been published on their functional capacity. METHODS: The frequency and number of circulating CD3+6B11+ iNKT cells and their CD4+ and CD4- subpopulations were evaluated in peripheral blood obtained from 41 patients with AD by four-color flow cytometry. Likewise, functional properties of iNKT cells were measured by five-color intracellular cytokine staining. RESULTS: The number and percentage of total iNKT cells and their CD4/CD8 subpopulations were significantly lower than the controls. Of further importance, the CD4-CD8- (double negative, DN) iNKT subgroup showed the strongest positive correlation with total iNKT cells. In addition, the DN subgroup exhibited the most pronounced functional alteration with significantly decreased levels of intracellular IFNγ and significantly increased levels of intracellular IL-4 in AD patients compared with the controls. CONCLUSION: The significantly altered number and cytokine production of iNKT cells from AD patients suggests that these cells may play an important role in the pathogenesis of AD.

Association between serum IL-16 levels and the degree of sensitization in patients with atopic dermatitis.

BACKGROUND: Interleukin (IL)-16 has been characterized as an immunomodulatory cytokine. Besides its chemotactic properties, IL-16 amplifies inflammatory processes and possesses immunoregulatory functions. Our aim was to investigate the association between serum IL-16 levels and the degree of allergic sensitization in patients with atopic dermatitis (AD). METHODS: The serum level of IL-16 was measured by immunoenzymatic assays. Eosinophil cell count, serum total and specific IgE levels were assessed; prick tests were also carried out. Based on specific IgE levels and prick tests, AD patients were divided into sensitized and nonsensitized subgroups, and correlations among serum IL-16, total IgE levels and eosinophil cell counts were measured in the total patient group and in subgroups. RESULTS: In the total patient group, significantly higher levels of IL-16 were found in the sera of patients with AD, compared to healthy individuals and patients with psoriasis. A significant correlation was detected between serum levels of IL-16 and total IgE, total IgE and eosinophil counts, but not between IL-16 and eosinophils. When sensitized and nonsensitized subgroups were compared, IL-16 levels showed a significant difference in subgroups that were divided based on specific IgE measurements, but not in those subgroups which were divided based on prick tests. On the other hand, serum total IgE levels showed a significant difference between sensitized and nonsensitized subgroups, assessed by the specific IgE method and also by prick test. CONCLUSION: Serum IL-16 levels of AD patients correlate to some extent with sensitization. This correlation is not as strong as the correlation between total IgE levels and allergic sensitization.

Alfacalcidol treatment restores derailed immune-regulation in patients with undifferentiated connective tissue disease.

Vitamin D deficiency may contribute to pathological changes in the number and function of CD4+ T helper cell subsets (CD4+Th1, CD4+Th17, CD4+CD25(bright)Foxp3-natural regulatory T cells-nTreg) in patients with undifferentiated connective tissue disease (UCTD). The aim of the present study was to evaluate, whether alfacalcidol could restore immune-regulatory changes in patients with UCTD. We assessed the optimal dose of alfacalcidol that could normalize the elevated levels of IFN-γ expressed by the CD4+Th1 cells and the IL-17 expressed by Th17 cells. Furthermore alfacalcidol decreased the Th1 and Th17 related cytokine levels, repaired the nTreg/Th7 balance, and restored the functional activity of nTreg cells. Twenty one UCTD patients with Vitamin D deficiency (<30 ng/ml) were administered with three different daily doses of alfacalcidol. Seven patients were supplemented with 0.5 µg/day, 7 patients with 1.0 µg/day, and 7 patients with 1.5 µg/day alfacalcidol treatment during 5 weeks. Our results indicated that 1.0 µg/day alfacalcidol during 5 weeks was the optimal therapeutic regime to increase the vitamin D levels, repair the nTreg/Th17 balance and raise the capacity of nTreg cells to suppress the proliferation of autologous CD4+CD25- cells. 1.5 µg daily dose alfacalcidol was not more effective than the 1.0 µg/day treatment. In this study we described that vitamin D deficiency can contribute to the complex immune-regulatory abnormalities in patients with UCTD and vitamin D substitution therapy can improve the fine balance of pro- and anti-inflammatory processes in the disease.

The immunoregulatory role of vitamins A, D and E in patients with primary Sjogren's syndrome.

OBJECTIVE: The aim of the present study was to investigate the immunomodulating role of fat-soluble vitamins in 25 patients with primary SS (pSS) and 15 healthy individuals. METHODS: Plasma levels of vitamins A, D and E were determined by HPLC. Peripheral NK, NK T cells, T-cell subsets, B cells, IL-10 producing Tr1 cells, CD4(+)CD25(+) Treg cells and Th17 were determined by flow cytometry. Various Th1- and Th2-soluble cytokines were assessed by ELISA, whereas intracytoplasmic cytokines (IFN-gamma, IL-4, -10 and -17) were measured by flow cytometry. Correlation was assessed between vitamin levels and immunological and clinical parameters. RESULTS: Vitamin A levels did not differ between patients and controls, yet in patients with extraglandular manifestations (EGMs) a significant decrease in vitamin A levels was apparent compared with pSS patients without EGMs (P = 0.005). Vitamin E levels were increased in patients compared with controls (P = 0.004), whereas vitamin D levels were similar in pSS and control subjects. In patients, vitamin A showed a positive correlation with both NK cell (P = 0.038) and Th17 cell (P = 0.025), and a negative correlation with Schirmer's test values (P = 0.035). Positive correlation was found between vitamin E and NK cells (P = 0.043), Th1 cells (P = 0.049) and the Th1/Th2 ratio (P = 0.043). In the control group, we found correlation between vitamin E and serum IL-10 levels (P = 0.003). CONCLUSIONS: Our data suggest that fat-soluble vitamins may be important in immunoregulatory processes in patients with pSS.

Vitamin D deficiency in undifferentiated connective tissue disease.

INTRODUCTION: Both experimental and clinical data provide evidence that vitamin D is one of those important environmental factors that can increase the prevalence of certain autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, insulin-dependent diabetes mellitus, and inflammatory bowel disease. The aim of the present study was to investigate the prevalence of vitamin D insufficiency in patients with undifferentiated connective tissue disease (UCTD). METHODS: Plasma 25(OH)D3 levels in 161 UCTD patients were measured in both summer and winter periods. Autoantibody profiles (antinuclear antibody, anti-U1-ribonucleoprotein, anti-SSA, anti-SSB, anti-Jo1, anti-Scl70, anti-double-stranded DNA, anti-centromere, anti-cardiolipin, rheumatoid factor, and anti-cyclic citrullinated peptide) and clinical symptoms of the patients were assessed. RESULTS: Plasma levels of 25(OH)D3 in UCTD patients were significantly lower compared with controls in both summer and winter periods (UCTD summer: 33 +/- 13.4 ng/mL versus control: 39.9 +/- 11.7 ng/mL, P = 0.01; UCTD winter: 27.8 +/- 12.48 ng/mL versus control: 37.8 +/- 12.3 ng/mL, P = 0.0001). The presence of dermatological symptoms (photosensitivity, erythema, and chronic discoid rash) and pleuritis was associated with low levels of vitamin D. During the average follow-up period of 2.3 years, 35 out of 161 patients (21.7%) with UCTD further developed into well-established connective tissue disease (CTD). Patients who progressed into CTDs had lower vitamin D levels than those who remained in the UCTD stage (vitamin D levels: CTD: 14.7 +/- 6.45 ng/mL versus UCTD: 33.0 +/- 13.4 ng/mL, P = 0.0001). CONCLUSIONS: In patients with UCTD, a seasonal variance in levels of 25(OH)D3 was identified and showed that these levels were significantly lower than in controls during the corresponding seasons. Our results suggest that vitamin D deficiency in UCTD patients may play a role in the subsequent progression into well-defined CTDs.

Sarcoidosis in patients with mixed connective tissue disease: clinical, genetic, serological and histological observations.

The objective of this study was to investigate how the development of sarcoidosis influences the disease course of mixed connective tissue disease (MCTD). The cellular composition of MCTD-associated sarcoidosis granulomas was evaluated and also the disease-accompanying T-cell activation and alterations of the serum cytokine levels were measured before and after the therapy. The HLA-DR specific alleles were also assessed. We present two cases with MCTD coexisting sarcoidosis. Serum concentrations of Th1 and Th2 cytokines were assessed by ELISA. Peripheral blood CD3+ total T-cell numbers, CD4+ and CD8+ T-cell subset were determined by flow cytometry. Furthermore, hematoxylin-eosin staining and immunhistochemistry were performed for histological assessment. HLA-DR specific alleles were determined by using PCR-SSP. Elevated number of activated T-cells and high Th1 cytokine levels were detected, mainly IFN-gamma and TNF-alpha. Histologically, CD4+ and CD8+ T-cells were present in the sarcoidosis infiltrations. The haplotypes were to some extent dissimilar from the HLA-DR genotype from patients with MCTD, or sarcoidosis alone. Sarcoidosis enhances the activation of MCTD, based on the laboratory and clinical findings. Our results show that the inflammation is mainly in the effector phase, while granuloma formation is characteristic of the resolution phase of the disease. The assessment of the cytokine network in sarcoidosis-associated MCTD enables us to select the most effective, individualized therapy protocol for these patients.

Clinical and laboratory examinations in the subgroups of chronic urticaria.

BACKGROUND: The aetiology of chronic urticaria is heterogeneous. Physical urticaria (PU) is estimated at around 35%, autoimmune urticaria (AIU) at 25% and chronic idiopathic urticaria (CIU) at 35% of all chronic urticaria cases. METHODS: Differences in clinical and laboratory parameters among AIU, PU and CIU groups were examined. AIU was diagnosed if the basophil CD63 assay was positive. Demographic data, severity of symptoms and association with allergic and autoimmune diseases were analysed by the aid of a questionnaire. Immunoassays were carried out and the effectiveness of therapy was also investigated. RESULTS: Concerning the urticaria score, AIU patients had significantly higher total urticaria scores than patients with CIU (p = 0.013), dermatographic urticaria (p = 0.05) or cholinergic urticaria (p = 0.038). Between CIU and dermatographic urticaria and between CIU and cholinergic urticaria patients, we found insignificant differences in the urticaria score (p = 0.707 and p = 0.336, respectively). AIU was more frequently associated with autoimmune diseases in the personal history (p < 0.001) and with other types of urticaria in the family history (p < 0.001). Also, anti-thyroid antibodies were more frequently detected in the AIU group. Antihistamine therapy was less effective in the AIU group (12.8%) than in the PU (70.3%) and CIU groups (68.6%), but there were no significant differences between the CIU and PU groups regarding the effectiveness of antihistamine therapy. CONCLUSION: The autoimmune subgroup represents the most severe form of chronic urticaria. On the other hand, there were no significant differences between the CIU and PU groups neither in urticaria scores nor in response to antihistamine therapy.

[The laboratory diagnosis of food allergies]. / Az ételallergiák laboratóriumi diagnosztikája.

This paper summarizes the most common allergens in Hungary, the various forms of food allergies, the tools of their diagnosis, with special respect to the possibilities of in vitro laboratory tests. These thoughts are in accordance with the position papers of European Academy of Allergology and Clinical Immunology and Hungarian College of Clinical Immunology and Allergology.

Elevated white blood cell count, CRP and fibrinogen levels are not associated with increased anti-endothelial and anti-ox-LDL antibody, MCP-1, and RANTES levels in early onset occlusive carotid artery disease.

BACKGROUND: Inflammatory processes have importance in atherosclerosis. We evaluated if subjects below 55 years of age with occlusive carotid artery disease have higher serum levels of antibodies against oxidized LDL and endothelial cells and the chemokines MCP-1 and RANTES than age matched subjects without atherosclerosis. METHODS AND RESULTS: Sixty patients with occlusive carotid artery disease (stenosis or occlusion) and 30 age-matched controls participated in the study. We measured the degree of carotid artery stenosis and intima-media thickness (IMT) by duplex ultrasound. White blood cell count (WBC), C-reactive protein (CRP), and fibrinogen levels were significantly higher in patients (means+/-SD: 7.5+/-1.8 vs. 6.1+/-1.1 G/L, p<0.001; 7.7+/-20.7 vs. 2.5+/-1.9 mg/L, p=0.015; and 3.7+/-0.9 vs. 3.1+/-0.5 g/L, p<0.001, respectively). Antibody levels against oxidized LDL and endothelial cells (21.1+/-22.9 and 19.9+/-15.3 EU/mL, p=0.6; and 19+/-15 vs. 20+/-9 U/mL, p=0.07) and RANTES and MCP-1 levels (72.4+/-32.3 vs. 73.8+/-27.3 ng/mL, p=0.7; and 468+/-1041 vs. 318+/-131 pg/mL, p=0.7) did not differ significantly between patients and controls and did not correlate with IMT. CONCLUSIONS: Higher levels of WBC, CRP, and fibrinogen suggest an ongoing inflammation in early-onset carotid atherosclerosis, but increased IMT is not associated by the elevation of serum levels of chemokines and antibodies evaluated in this study.

[Increased IgE-type antibody response to food allergens in irritable bowel syndrome and inflammatory bowel diseases]. / Fokozott IgE típusú antitestválasz ételallergénekkel szemben irritábilis bél szindrómában és gyulladásos bélbetegségekben.

BACKGROUND: The irritable bowel syndrome (IBS) is a functional bowel disorder characterized by symptoms of abdominal pain that is associated with disturbed defecation. Crohn's disease (CD) and Ulcerative colitis (UC) are collectively referred to as inflammatory bowel diseases (IBD). IBD appears to result from dysregulated immune response with contributions from genetic predisposition and environmental factors. Among environmental factors the enteric microflora and the components of food (eg. antigens) may play important role in the pathogenesis of IBD. The aim of the authors' study was to detect IgE type antibodies against the most frequent food allergens in patients with IBD and IBS. METHODS: Antibodies against food allergens (IgE type) with ELISA method in patients with CD, UC and IBS were quantitatively measured. The figures were compared to the result of a healthy control group contains the same number of participants, and the frequency of food allergy in these patient groups were determined. RESULTS: On the basis of the study the presence of increased IgE type immune response against any food allergens was 34.5% (p = 0.01) in the group of IBS. In patients with CD or UC the immune response against food allergens was also more frequent than in the control group. The order of frequency of food allergens in IBS was the following: milk protein, soybean, tomato, peanut, egg white. CONCLUSION: As the occurrence of food allergens was significantly higher in IBS group than in the control group, the role of food allergy in the symptoms of IBS can be come up. The frequency of food allergy in patients with diagnosis of IBS, and the similarity of symptoms of this two diseases give an obvious opportunity for the patients with IBS to use a diet avoiding the most frequent food allergens, or take e.g. Na-cromoglycate which is useful therapy in food allergy.