Prevalence and epidemiological profile of celiac disease in children with type 1 diabetes mellitus: Experience from a tertiary care center of India.

BACKGROUND: The HLA associations of celiac disease (CD) in north Indians differ from that in Europeans. Our dietary gluten is among the highest in the world. Data on CD in people with diabetes (PWD) in north India is scant. OBJECTIVE: To estimate the prevalence and clinical profile of CD in children with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Retrospective review of case records of PWD with onset ≤18 years of age, registered between 2009 and 2020, having at least one anti tissue-transglutaminase (anti-tTG) serology report. RESULTS: Of 583 registered PWD, 398 (68.2%) had celiac serology screening. A positive report was obtained in 66 (16.6%). Of 51 biopsied people, 22 (5.5%) were diagnosed to have CD, 12 in the first 2 years of diabetes onset. Symptomatic CD at diagnosis was seen in 63% (14/22). Age at diabetes onset (median [IQR] age 5.5 years, [2-12]) was lower in PWD and CD compared to PWD alone (10 years, [7-14], p < 0.016). Of 36 biopsied children with anti-tTG >100 au/ml, 20 (55.5%) had CD, while 2 out of 15 (13.3%) of those with lower anti-tTG titer had histopathology suggestive of CD. Of 23 seropositive children not diagnosed with CD, 5 of 8 with anti tTG >100 au/ml, and all 15 with lower anti-tTG, had normalization of titers over the 24 (10-41) months. CONCLUSIONS: Our prevalence of CD is comparable to international data. Celiac disease was common with younger age at onset of T1D and higher titer of celiac serology. A high proportion was symptomatic of CD at diagnosis.

Diagnostic utility of multiple site duodenal biopsies in celiac disease.

BACKGROUND: Celiac Disease involves the small intestine patchily affecting more frequently the proximal small bowel but the histological changes have been observed till terminal ileum. Of late in addition to D2, the duodenal bulb (D1 region) biopsies have been found helpful in identifying a small group of patients with CD. Therefore, multiple site biopsies are recommended as histological changes are not uniform throughout small intestine. METHODS: During this present 1.5 years prospective study, we evaluated 84 cases of suspected celiac disease with respect to the light microscopy (D1, D2, and D3 biopsy) and serology (anti tTg and or EMA). Histological examination was done according to Modified Marsh grading system. RESULTS: Out of 84 cases with raised anti tTg, the segmental biopsies significantly increased the diagnostic accuracy from 39/44 cases (88.6%) to 43/44 cases (97.7%) and 44/44 cases (100%) when D2 alone, D1 + D2 and D1 + D2 + D3 biopsies were evaluated, respectively. Of the suspected cases of celiac disease patients (tTg > 10 ULN and associated weight loss, diarrhea), additional D3 biopsy increased the diagnostic yield by 2.1%, compared to D1, D2 region biopsy and 6.38% compared to standard D2 biopsy alone. Of the 28 cases (tTg > 10 times ULN + EMA positive and associated weight loss, diarrhea), the potential celiac disease (histologically Type 1/Normal) cases reduced from 28.5% (standard D2 region alone) to 21.4% and 17.8% when additional biopsies were taken from D1 region and D3 region, respectively, and additional D3 biopsy increased the diagnostic yield by 10.8% (compared to standard D2 biopsy alone) and 3.7% (compared to D1 and D2 biopsy). CONCLUSION: We believe multiple sites duodenal biopsies including D3 region biopsies might increase the diagnostic accuracy of adult celiac disease in addition to sensitive and specific serologic tests.

Refractory celiac disease type II: An atypical case highlighting limitations of the current classification system.

Refractory celiac disease (RCD) is a rare condition associated with high morbidity that develops in individuals with celiac disease. It is known to be biologically heterogeneous, and currently two types are recognized based on immunophenotypic and molecular features, type I (RCD I) and type II (RCD II). Differentiating between RCD I and RCD II is critical, as patients with RCD II have substantially worse outcomes and a high risk of developing enteropathy-associated T-cell lymphoma. However, the current RCD classification is limited in scope, and atypical presentations and immunophenotypes are not recognized at present. Herein, we describe a unique case of RCD II with atypical clinical (primarily neurologic manifestations and lack of significant gastrointestinal symptoms), histopathologic (no villous atrophy), immunophenotypic (virtual absence of cytoplasmic CD3 expression), and molecular features (absence of clonal TR rearrangement and identification of pathogenic STAT3 and KMT2D mutations). This case highlights limitations of the current RCD classification system and the utility of next generation sequencing (NGS) studies in the diagnostic workup of RCD. Future algorithms need to recognize extraintestinal manifestations and incorporate atypical histopathologic and immunophenotypic features, as well as results of NGS analysis for RCD II classification.

Small-bowel carcinomas associated with celiac disease: transcriptomic profiling shows predominance of microsatellite instability-immune and mesenchymal subtypes.

Celiac disease (CD) is a risk factor for developing small-bowel carcinoma with a 14-fold higher risk compared with general population. As small-bowel carcinomas associated with CD (CD-SBCs) are extremely rare, very few molecular data are available about their pathogenesis, and information about their transcriptomic profiling is lacking. We generated RNA-seq data on 13 CD-SBCs, taken from the largest well-characterized series published so far, collected by the Small Bowel Cancer Italian Consortium, and compared the tumor transcriptional signatures with the four Consensus Molecular Subtypes (CMS) of colorectal carcinoma by applying the "CMS classifier." CpG Island Methylator Phenotype (CIMP) was evaluated using methylation-sensitive multiple ligation-dependent probe amplification. Up to 12 of 13 cancers fell within the two main subtypes exhibiting high immune and inflammatory signatures, i.e., subtypes 1 and 4. The first and predominant subset was commonly microsatellite unstable, and exhibited CIMP and high CD3+ and CD8+ T cell infiltration. Moreover, it showed increased expression of genes associated with T helper 1 and natural killer cell infiltration, as well as upregulation of apoptosis, cell cycle progression, and proteasome pathways. By contrast, cancers falling in subtype 4 showed prominent transforming growth factor-ß activation and were characterized by complement-associated inflammation, matrix remodeling, cancer-associated stroma production, and angiogenesis. Parallel histologic and histochemical analysis confirmed such tumor subtyping. In conclusion, two molecular subtypes have been consistently identified in our series of CD-SBCs, a microsatellite instability-immune and a mesenchymal subtype, the former likely associated with an indolent and the latter with a worse tumor behavior.

Duodenal mucosal immune cells in treatment-naive adult patients with celiac disease having different histological grades and controls.

BACKGROUND: It is hypothesized that the duodenal mucosal damage in patients with celiac disease (CeD) is caused by the mucosa-infiltrating lymphoid cells. This study aimed to analyze the immune effective and regulatory T (Treg) cells in duodenal biopsies from treatment-naive adult patients with CeD having different histological grades and controls. PATIENTS AND METHODS: Dual-color immunohistochemical staining was done in a total of 234 duodenal biopsies, including 132 controls and 102 adult patients with CeD using CD20, CD3:CD4, CD3:CD8, CD4:FoxP3, CD8:FoxP3, and TCRαß:TCRγδ antibodies. The density of these lymphoid cells in lamina propria and mucosal epithelium was compared between controls and CeD, with different modified Marsh grades. RESULTS: Densities of CD4+ T cells in lamina propria and CD8+γδ intraepithelial lymphocytes (IELs) were significantly more in biopsies from patients with CeD, than in controls. An increasing linear pattern of IELs, CD3+ T cells, and CD20+ B cells was observed with increasing grades of villous abnormalities. Although CD8+ FoxP3+ Treg cells were significantly more in biopsies from patients with CeD, there was no significant difference in CD4+ FoxP3+ Treg cell infiltrate between both the groups. CONCLUSION: Our finding in this observational study generates interest to study the local intestinal mucosal immunity in CeD in detail. A study to prove the failure of CD4+ FoxP3+ Treg cell recruitment in CeD and its direct functional impact may yield valuable information regarding loss of mucosal tolerance.

Diagnosing celiac disease: A critical overview.

The diagnosis of celiac disease (CD) no longer rests on a malabsorptive state or severe mucosal lesions. For the present, diagnosis will always require the gold-standard of a biopsy, interpreted through its progressive phases (Marsh classification). Marsh classification articulated the immunopathological spectrum of gluten-induced mucosal changes in association with the recognition of innate (Marsh I infiltration) and T cell-based adaptive (Marsh II, and the surface re-organisation typifying Marsh III lesions) responses. Through the Marsh classification the diagnostic goalposts were considerably widened thus, over its time-course, permitting countless patients to begin a gluten-free diet but who, on previous criteria, would have been denied such vital treatment. The revisions of this classification failed to provide additional insight in the interpretation of mucosal pathology. Morever, the subclassification of Marsh 3 imposed an enormous amount of extra work on pathologists with no aid in diagnosis, treatment, or prognosis. Therefore, it should now be apparent that if gastroenterologists ignore these sub-classifications in clinical decision-making, then on that basis alone, there is no need whatsoever for pathologists to persist in reporting them. Since new treatments are under critical assessment, we might have to consider use of some other higher level histological techniques sensitive enough to detect the changes sought. A promising alternative would be to hear more voices from imaginative histopathologists or morphologists together with some more insightful approaches, involving molecular-based techniques and stem cell research may be to evaluate mucosal pathology in CD.

Distinct phenotype of CD4+ T cells driving celiac disease identified in multiple autoimmune conditions.

Combining HLA-DQ-gluten tetramers with mass cytometry and RNA sequencing analysis, we find that gluten-specific CD4+ T cells in the blood and intestines of patients with celiac disease display a surprisingly rare phenotype. Cells with this phenotype are also elevated in patients with systemic sclerosis and systemic lupus erythematosus, suggesting a way to characterize CD4+ T cells specific for disease-driving antigens in multiple autoimmune conditions.

Celiac disease gene expression data can be used to classify biopsies along the Marsh score severity scale.

BACKGROUND AND AIM: The diagnosis of celiac disease autoimmune pathology relies on the subjective histological assignment of biopsies into Marsh score categories. It is hypothesized that Marsh score categories have unique gene expression signatures. The aims were as follows: first, to develop a celiac disease quantitative reverse transcription-polymerase chain reaction (RT-PCR) array; second, define gene expression signatures associated with Marsh score categories; and third, develop equations that classify biopsies into Marsh score categories and to monitor the efficacy of patient treatment. METHODS: Gene targets for inclusion in the celiac RT-PCR (qRT-PCR) array were identified using systematic analysis of published celiac transcriptomic data. The array was used to assess the gene expression associated with histological changes in duodenal biopsies obtained from adult patients. Finally, Marsh score classification equations were defined using discriminant analysis. RESULTS: The array contained 87 genes. The expression of 26 genes were significantly (p < 0.06) associated with the discrete Marsh score categories. As the Marsh score pathology of biopsies increased, there was a progression of innate immune gene expression through adaptive Th1-specific gene expression with a concurrent decrease in intestinal structural gene expression in high Marsh score samples. These 26 genes were used to define classification equations that accounted for 99% of the observed experimental variation and which could classify biopsies into Marsh score categories and monitor patient treatment progression. CONCLUSIONS: This proof-of-concept study successfully developed a celiac RT-PCR array and has provided evidence that discriminant equations defined using gene expression data can objectively and accurately classify duodenal biopsies into Marsh score categories.

Collagenous Enteritis is Unlikely a Form of Aggressive Celiac Disease Despite Sharing HLA-DQ2/DQ8 Genotypes.

Collagenous enteritis is an uncommon small intestinal injury pattern with unclear pathogenesis. While it has been speculated that collagenous enteritis represents a form of refractory celiac disease, recent clinical studies suggest a potential link to exposure to the antihypertensive medication olmesartan. Here we hypothesized that the pathogenesis of collagenous enteritis involves both genetic and environmental factors. All subjects with biopsy-proven collagenous enteritis diagnosed between 2002 and 2015 were identified from 2 tertiary care medical centers. Human leukocyte antigen (HLA)-DQ genotyping was performed by polymerase chain reaction on archived tissue. Celiac disease serology, past medical history, medications, smoking history, demographics, histology, clinical management, and follow-up were recorded. A total of 32 subjects were included. In contrast to celiac disease, subjects with collagenous enteritis were mostly elderly (median age at diagnosis, 69 y; range, 33 to 84 y). Seventy percent of collagenous enteritis subjects harbored celiac disease susceptibility alleles HLA-DQ2/DQ8; however, only 1 subject had elevated serum levels of celiac disease-associated autoantibodies while on a gluten-containing diet. Furthermore, 56% of subjects were taking nonsteroidal anti-inflammatory drugs, 36% proton-pump inhibitors, 28% statins, and 32% olmesartan at the time of diagnosis. Discontinuation of olmesartan and treatments with steroids and/or gluten-free diet resulted in symptomatic and histologic improvement. Neither lymphoma nor collagenous enteritis-related death was seen in this cohort. Therefore, while collagenous enteritis shares similar HLA genotypes with celiac disease, the difference in demographics, the lack of celiac disease-associated autoantibodies, and potential link to medications as environmental triggers suggest the 2 entities are likely distinct in pathogenesis.

T-cell repertoires in refractory coeliac disease.

OBJECTIVE: Refractory coeliac disease (RCD) is a potentially hazardous complication of coeliac disease (CD). In contrast to RCD type I, RCD type II is a precursor entity of enteropathy-associated T-cell lymphoma (EATL), which is associated with clonally expanding T-cells that are also found in the sequentially developing EATL. Using high-throughput sequencing (HTS), we aimed to establish the small-intestinal T-cell repertoire (TCR) in CD and RCD to unravel the role of distinct T-cell clonotypes in RCD pathogenesis. DESIGN: DNA extracted from duodenal mucosa specimens of controls (n=9), active coeliacs (n=10), coeliacs on a gluten-free diet (n=9), RCD type I (n=8), RCD type II (n=8) and unclassified Marsh I cases (n=3) collected from 2002 to 2013 was examined by TCRß-complementarity-determining regions 3 (CDR3) multiplex PCR followed by HTS of the amplicons. RESULTS: On average, 106 sequence reads per sample were generated consisting of up to 900 individual TCRß rearrangements. In RCD type II, the most frequent clonotypes (ie, sequence reads with identical CDR3) represent in average 42.6% of all TCRß rearrangements, which was significantly higher than in controls (6.8%; p<0.01) or RCD type I (6.7%; p<0.01). Repeat endoscopies in individual patients revealed stability of clonotypes for up to several years without clinical symptoms of EATL. Dominant clonotypes identified in individual patients with RCD type II were unique and not related between patients. CD-associated, gliadin-dependent CDR3 motifs were only detectable at low frequencies. CONCLUSIONS: TCRß-HTS analysis unravels the TCR in CD and allows detailed analysis of individual TCRß rearrangements. Dominant TCRß sequences identified in patients with RCD type II are unique and not homologous to known gliadin-specific TCR sequences, supporting the assumption that these clonal T-cells expand independent of gluten stimulation.

Enfermedad celíaca y otras patologías relacionadas con el gluten / Celiac disease and other pathologies related to gluten

Se intentan aclarar los conceptos diferenciales de enfermedad celíaca, sensibilidad al gluten no celíaca y alergia al trigo. Se abordan las manifestaciones clínicas junto al Score clínico desarrollado en el Servicio para calcular matemáticamente la presencia de enfermedad celíaca. Finalmente, se aborda el tartamiento, seguimiento, y las nuevas patologías relacionadas a la enfermedad

A New Proposal for the Pathogenic Mechanism of Non-Coeliac/Non-Allergic Gluten/Wheat Sensitivity: Piecing Together the Puzzle of Recent Scientific Evidence.

Non-coeliac/non-allergic gluten/wheat sensitivity (NCG/WS) is a gluten-related disorder, the pathogenesis of which remains unclear. Recently, the involvement of an increased intestinal permeability has been recognized in the onset of this clinical condition. However, mechanisms through which it takes place are still unclear. In this review, we attempt to uncover these mechanisms by providing, for the first time, an integrated vision of recent scientific literature, resulting in a new hypothesis about the pathogenic mechanisms involved in NCG/WS. According to this, the root cause of NCG/WS is a particular dysbiotic profile characterized by decreased butyrate-producing-Firmicutes and/or Bifidobacteria, leading to low levels of intestinal butyrate. Beyond a critical threshold of the latter, a chain reaction of events and vicious circles occurs, involving other protagonists such as microbial lipopolysaccharide (LPS), intestinal alkaline phosphatase (IAP) and wheat α-amylase trypsin inhibitors (ATIs). NCG/WS is likely to be a multi-factor-onset disorder, probably transient and preventable, related to quality and balance of the diet, and not to the presence of gluten in itself. If future studies confirm our proposal, this would have important implications both for the definition of the disease, as well as for the prevention and therapeutic-nutritional management of individuals with NCG/WS.

[All-Russian Consensus on Diagnosis and Treatment of Celiac Disease in Children and Adults]. / Vserossiiskii konsensus po diagnostike i lecheniyu tseliakii u detei i vzroslykh.

The paper presents the All-Russian consensus on the diagnosis and treatment of celiac disease in children and adults, which has been elaborated by leading experts, such as gastroenterologists and pediatricians of Russia on the basis of the existing Russian and international guidelines. The consensus approved at the 42nd Annual Scientific Session of the Central Research Institute of Gastroenterology on Principles of Evidence-Based Medicine into Clinical Practice (March 2-3, 2016). The consensus is intended for practitioners engaged in the management and treatment of patients with celiac disease. Evidence for the main provisions of the consensus was sought in electronic databases. In making recommendations, the main source was the publications included in the Cochrane Library, EMBASE, MEDLINE, and PubMed. The search depth was 10 years. Recommendations in the preliminary version were reviewed by independent experts. Voting was done by the Delphic polling system.

The Severity of Symptoms Related to Irritable Bowel Syndrome is a Risk Factor for the Misclassification of Significant Organic Disease.

BACKGROUND AND AIMS: The diagnosis of irritable bowel syndrome (IBS) is based mainly on clinical evaluation. The reported incidence of misclassification of significant organic diseases in previously diagnosed IBS patients differs between studies. The aim of this study was to examine the incidence and risk factors for the misclassification of significant organic disease [colon cancer, inflammatory bowel disease (IBD), Celiac disease, and thyroid dysfunction] in a cohort of young patients with symptoms attributed to IBS. METHODS: In this population-based cohort study, we examined the incidence and risk factors for the diagnosis of a new significant organic diseases in a cohort of 2645 IBS patients. RESULTS: During follow-up, organic disease was diagnosed in 27 subjects (1.03%): IBD in 23, Celiac disease in 2, IBD and Celiac disease in 1, and hypothyroidism in1. The mean interval from the diagnosis of IBS to the diagnosis of an organic disorder was 13.08±8.51 months. Increased symptom severity was the only significant risk factor for the misclassification of an organic disease (hazard ratio, 2.26; 95% confidence interval, 1.01-5.05; P=0.047). The risk ratio for misclassification of organic diseases in moderate to severe IBS was increased by 2.575 (95% confidence interval, 1.10-6.51; P=0.027) as compared with mild IBS. CONCLUSIONS: The incidence of misclassification of major organic disease in IBS patients was low. Increased symptoms severity was the only significant risk factor for the misclassification of organic disorders. Further gastrointestinal evaluation should be considered in patients with moderate to severe symptoms attributed to IBS.

Classification chaos in coeliac disease: Does it really matter?

The spectrum of mucosal pathology in coeliac disease (CD), initially defined by Marsh in 1992 has been subjected to several modifications in the following years by Oberhuber, then by Corazza and Villanaci, and finally by Ensari. The present study, aimed to end the ongoing confusion regarding the classification of mucosal pathology in CD by applying all the classifications proposed so far on a large series of cases. A total of 270 duodenal biopsies taken from the distal duodenum of patients with a diagnosis of CD were included in the study. All biopsies were classified according to Marsh, Oberhuber, Corazza Villanaci, and Ensari classification schemes. For statistical analyses cases were divided into three groups: Group 1 included type 1 lesions in Marsh, Ensari, and Oberhuber and grade A in Corazza Villanaci classifications. Group 2 comprised of type 2 lesions in Marsh and Ensari classifications together with type2, type 3a and 3b lesions in Oberhuber classification and grade B1 lesions in Corazza Villanaci classification. Group 3 included type 3 lesions in Marsh and Ensari classifications, and type 3c lesions in Oberhuber, and grade B2 lesions in Corazza Villanaci classifications. The kappa value was 1.00 (excellent) for group 1, 0.53 (fair) for group 2 and 0.78 (excellent) for group 3 (p<0.0001). These results suggest that any of the above classification system would serve similar purposes in the diagnosis of CD. Therefore, it is advisable that the pathologist should use the simplest reliable scheme.

[Non-allergic gluten sensitivity. A controversial disease - or not yet sufficiently explored?]. / Nichtallergische Glutensensitivität. Ein umstrittenes Krankheitsbild - oder noch nicht ausreichend erforscht?

The avoidance of wheat, gluten and other cereal products is a growing phenomenon in industrialized countries. The diagnostic criteria of celiac disease and of food allergy to wheat flour and/or other cereals are clearly defined. Only about 0.5-25 % of the population are affected from both of these immunological diseases.Nevertheless, there exists a significantly greater proportion of people reporting at least subjectively significant complaints and quality of life improvements after switching to a wheat- or gluten-free diet. Celiac disease or wheat allergy cannot be detected in these individuals on the basis of established criteria. The absence of clear diagnostic autoimmune or allergic criteria in these wheat sensitive patients has resulted in the description of non-celiac gluten sensitivity.It is clinically detectable in only very few individuals and may manifest with either intestinal, extra-intestinal or neurovegetative and psychosomatic symptoms, respectively. However, non-celiac disease gluten sensitivity has to be differentiated critically from irritable bowel syndrome, carbohydrate malassimilation, postinfectious conditions and psychosomatic diseases.Pathophysiologically, non-celiac disease gluten sensitivity is still poorly characterized; several non-immunological mechanisms are discussed to contribute to non-celiac gluten sensitivity. These include the effects of fructo- and galacto-oligosaccharides, of trypsin inhibitors of amylase, and wheat lectin agglutinins, which may influence or modulate intestinal permeability and/or a non-specific immune or effector cell degranulation within the gastrointestinal tract. In addition, further metabolic effects with direct or indirect influence on the intestinal flora are currently discussed.In addition to subjectively reported changes in symptoms that may affect variably intestinal, as well as extra-intestinal and/or neuropsychiatric symptoms, some studies suggest that there is little reproducibility of complaints from gluten exposure. For a definitive diagnosis of non-celiac gluten sensitivity, structured (blinded) challenge tests with wheat or gluten are mandatory as well as re-challenge after a defined time of gluten avoidance to establish non-celiac disease gluten sensitivity as a persistent disease entity.

Is a detailed grading of villous atrophy necessary for the diagnosis of enteropathy?

AIMS: The utility of the 7 level Marsh-Oberhuber classification of mucosal damage in patients with coeliac disease has recently been criticised. Analysis of duodenal biopsies with dissecting microscopy is an unsophisticated method that, however, provides useful information in cases of frank villous atrophy. In the last 15 years, we have always analysed duodenal biopsies with dissecting microscopy before sending them to the pathology department for histology. If the results of dissecting microscopy and traditional histology were comparable, we feel that would be strong evidence that grading of the histological lesion would be unnecessary if not pointless in the everyday diagnosis of enteropathies. METHODS: The clinical notes of all 2075 patients undergoing duodenal biopsy between September 1999 and June 2015 were retrospectively analysed. Results of duodenal mucosal evaluation with both dissecting microscopy and traditional histology were collected and statistically compared. RESULTS: The κ statistics showed a substantial agreement of the two methods (κ statistics 0.78). Sensitivity of dissecting microscopy for detection of severe villous atrophy was 85.1% (95% CI 81.2% to 88.5%) and specificity was 95% (95% CI 93.8% to 96%). CONCLUSIONS: Although dissecting microscopy is an unsophisticated method that obviously cannot substitute traditional histology, our results suggest that in everyday clinical practice, the diagnosis of coeliac disease and other flat enteropathies does not require grading of villous atrophy.

Prevalence of celiac disease and related antibodies in patients diagnosed with irritable bowel syndrome according to the Rome III criteria. A case-control study.

BACKGROUND: The cost-effectiveness for screening for celiac disease (CD) in patients with irritable bowel syndrome (IBS), specifically in the diarrhea (IBS-D) subtype, is beneficial if the prevalence is >1%. However, recent studies have shown controversial results. In this large case-control study, our aim was to determine the prevalence of CD and a panel of related antibodies in patients diagnosed with IBS. MATERIALS AND METHODS: Four hundred IBS patients (Rome III) and 400 asymptomatic healthy controls were prospectively evaluated using antihuman tissue transglutaminase (h-tTG IgA) and deamidated gliadin peptide antibodies (DGP II IgA and DGP II IgG). Duodenal biopsy was performed on the patients that were positive for the h-tTG IgA and/or DGP II IgG antibodies. RESULTS: The mean age of the population was 44.47 ± 18.01 years and 335 (82%) of the subjects were women. Twenty-one patients and six controls had at least one positive test for CD (5.25% VS 1.5%, p = 0.003, OR 3.63 [95% CI 1.4-9.11]). Eighteen patients were positive for h-tTG and/or DGP-II IgG. Histologic confirmation of CD was 2.5% in the IBS patients vs 0.5% in the controls (p = 0.04, OR 5.21). The IBS-D subtype had the highest prevalence for serological positivity (12.7%). CONCLUSIONS: Up to 5.2% of the patients with IBS according to the Rome III criteria were positive for at least one of the CD-related antibodies and 2.5% had biopsy-confirmed CD. Therefore, in our population, screening for CD in subjects with IBS appears to be a reasonable strategy, especially in the IBS-D subgroup.