Associations of dietary patterns between age 9 and 24 months with risk of celiac disease autoimmunity and celiac disease among children at increased risk.

BACKGROUND: Higher gluten intake in childhood is associated with increased incidence of celiac disease autoimmunity (CDA) and celiac disease. It remains to be studied whether different dietary patterns independent of gluten intake contribute to the incidence. OBJECTIVES: This study aimed to explore associations of dietary patterns by age 2 y with risk of CDA and celiac disease in genetically susceptible children. METHODS: Data was used from 6726 participants at genetic risk of type 1 diabetes and celiac disease enrolled in the observational cohort, The Environmental Determinants of Diabetes in the Young (TEDDY) study. Children were annually screened for tissue transglutaminase autoantibodies (tTGAs) from age 2 y. Principal component analysis extracted dietary patterns, based on intake of 27 food groups assessed by 3-d food records at age 9 to 24 mo. The primary outcome was CDA (i.e., persistently tTGA-positive in at least 2 consecutive samples), and the secondary outcome was celiac disease. During follow-up to mean age 11.0 (standard deviation 3.6) y, 1296 (19.3%) children developed CDA, and 529 (7.9%) were diagnosed with celiac disease. Associations of adherence to dietary patterns (per 5-unit increase) with the study outcomes were estimated by Cox regression models adjusted for risk factors including gluten intake. RESULTS: At age 9 mo, a dietary pattern higher in the food groups vegetable fats and milk was associated with reduced risk of CDA (hazard ratio [HR]: 0.88; 95% confidence interval [CI]: 0.79, 0.98; P = 0.02). At 24 mo, a dietary pattern higher in the food groups wheat, vegetable fats, and juices, and lower in milk, meat, and oats at age 24 mo was associated with increased risk of CDA (HR: 1.18; 95% CI: 1.05, 1.33; P < 0.001) and celiac disease (HR: 1.24; 95% CI: 1.03, 1.50; P = 0.03). CONCLUSIONS: Dietary patterns in early childhood are associated with risk of CDA and celiac disease in genetically predisposed children, independent of gluten intake.

Prediction of celiac disease associated epitopes and motifs in a protein.

Introduction: Celiac disease (CD) is an autoimmune gastrointestinal disorder causes immune-mediated enteropathy against gluten. Gluten immunogenic peptides have the potential to trigger immune responses which leads to damage the small intestine. HLA-DQ2/DQ8 are major alleles that bind to epitope/antigenic region of gluten and induce celiac disease. There is a need to identify CD associated epitopes in protein-based foods and therapeutics. Methods: In this study, computational tools have been developed to predict CD associated epitopes and motifs. Dataset used for training, testing and evaluation contain experimentally validated CD associated and non-CD associate peptides. We perform positional analysis to identify the most significant position of an amino acid residue in the peptide and checked the frequency of HLA alleles. We also compute amino acid composition to develop machine learning based models. We also developed ensemble method that combines motif-based approach and machine learning based models. Results and Discussion: Our analysis support existing hypothesis that proline (P) and glutamine (Q) are highly abundant in CD associated peptides. A model based on density of P&Q in peptides has been developed for predicting CD associated peptides which achieve maximum AUROC 0.98 on independent data. We discovered motifs (e.g., QPF, QPQ, PYP) which occurs specifically in CD associated peptides. We also developed machine learning based models using peptide composition and achieved maximum AUROC 0.99. Finally, we developed ensemble method that combines motif-based approach and machine learning based models. The ensemble model-predict CD associated motifs with 100% accuracy on an independent dataset, not used for training. Finally, the best models and motifs has been integrated in a web server and standalone software package "CDpred". We hope this server anticipate the scientific community for the prediction, designing and scanning of CD associated peptides as well as CD associated motifs in a protein/peptide sequence (https://webs.iiitd.edu.in/raghava/cdpred/).

Prevalence of haplotype DQ2/DQ8 and celiac disease in children with type 1 diabetes.

Type 1 diabetes (T1D) and celiac disease (CD) coexist very often. Identification of the human leukocyte antigen (HLA) DQ2/DQ8 can confirm the genetic predisposition to CD. Negative result of this test allows to exclude CD with a high probability. It was suggested that in individuals with higher risk of CD, including T1D patients, the implementation of genetic testing should reduce the number of patients requiring systematic immunological screening. The aim of this study was to analyze the prevalence of different haplotypes predisposing to CD in children and adolescents with previously diagnosed T1D. MATERIAL AND METHODS: A retrospective analysis was performed on 166 T1D children (91 girls) in whom HLA DQ2/DQ8 alleles were tested. In 9.6% CD was also diagnosed. RESULTS: In 12.7% both HLA DQ2/DQ8 were negative. In 87.3% patients HLA DQ2 and/or DQ8 was positive, including 27.7% patients with both haplotypes DQ2.5 and DQ8 positive. In all CD patients the disease predisposing alleles were positive, while none of the HLA DQ2/DQ8 negative children were diagnosed with CD. CONCLUSIONS: The prevalence of HLA DQ2.5 and the HLA DQ2.5 / HLA DQ8 configuration is higher in patients with T1D, and CD compared to children with T1D alone. The combination of HLA DQ2 and HLA DQ8 most significantly increases the risk of developing CD. The group of HLA DQ2/DQ8 negative patients with improbable CD diagnosis, is relatively small. Most of T1D patients HLA DQ2/DQ8 positive need further regular antibody assessment. In patients with T1D, who are at high risk of developing CD, genetic testing may be considered to select those who require further systematic serological evaluation. Due to its retrospective nature, the study was not registered in the database of clinical trials and the Clinical trial registration number is not available.

Possible effect of the HLA-DQ2/DQ8 polymorphism on autoimmune parameters and lymphocyte subpopulation in recurrent pregnancy losses.

Recurrent pregnancy loss (RPL) affects 1-2 % of women. Allo- and autoimmune disorders are a recognized factor for RPL and poor pregnancy outcomes. There is a link between antiphospholipid syndrome (APS), Hashimoto's thyroiditis or coeliac disease, and pregnancy losses. The prevalence of the HLA-DQ2/DQ8 polymorphism and genetic susceptibility to the development of celiac disease may be higher in women who experience RPL. A total of 95 women who had experienced two or more miscarriages were qualified into the study: 49 women with the HLA-DQ2/DQ8 polymorphism as the study group, and 46 as the control group. The prenatal test results of the women were evaluated, which revealed that the foetuses from the study group had higher nuchal translucency measurements than those of controls (1.85 mm vs 1.50 mm; p = 0.0024). A higher level of anticardiolipin antibodies (aCL) in the IgG class (18.38 GP L vs 11.37 GP L; p = 0.0039) and antithyroid peroxidase antibodies (aTPO) (87.67 IU/mL vs 11.87 IU/mL; p = 0.0062) was observed when compared to the control group. The presence of the HLA-DQ2.2 polymorphism was observed when higher nuchal translucency measurements and a higher aTPO concentration occurred. A relationship between the aTPO concentration and a higher birth weight of newborns was also shown. No significant differences between the groups were observed for peripheral blood lymphocyte subsets. A statistically significant relationship between the HLA-DQ2/DQ8 polymorphism and the increased concentrations of indicators of autoimmune disorders was indicated.

Celiac disease in pediatric patients according to HLA genetic risk classes: a retrospective observational study.

BACKGROUND: Celiac disease (CD) is an autoimmune enteropathy in which HLA-DQ haplotypes define susceptibility. Our aim was to evaluate if belonging to a certain HLA-DQ class risk could be associated to the clinical, serological and histological presentation of CD. METHODS: We performed a retrospective observational monocentric study including all 300 patients diagnosed with CD, who underwent HLA typing. Clinical, serological and histological data was collected from clinical records and their association with HLA-DQ class risk was verified through statistical tests. RESULTS: In our sample mean age at onset was 6.7 ± 4.2 years, with a prevalence of females (n = 183; 61%), typical symptoms (n = 242; 80.6%) and anti-tTG IgA ≥ 100 U/mL (n = 194; 64.7%). Family history was present only in 19% (n = 57) of patients, and it was not significantly associated with any of the clinical and demographical data analyzed or the belonging to a certain HLA-DQ class risk. We found in the male population more frequently a coexistence of CD and atopic syndrome (males: n = 47; 40.2%; females: n = 50; 27.3%; p = 0.020). Early age of onset, instead, was associated with typical symptoms (m = 6.4 ± 4; p = 0.045) and elevated liver enzymes (m = 5 ± 3.8; p < 0.001), while later age of onset was associated with presence of other autoimmune diseases (m = 8.2 ± 4; p = 0.01). We observed statistically significant influences of HLA class risk on antibodies and liver enzymes levels: G1, G4 and G2 classes showed more frequently anti-tTG IgA ≥ 100 U/mL (n = 44; 80%, n = 16; 69.6%, n = 48; 67.6% respectively; p-value = 0.037), and in patients from G2 class we found enhanced liver enzymes (n = 28; 39.4%; p-value = 0.005). HLA class risk was still significantly associated with anti-tTG ≥ 100 (p = 0.044) and with hypertransaminasemia (p = 0.010) after a multiple logistic regression adjusted for the effect of gender, age at onset and family history. CONCLUSIONS: We failed to prove an association between HLA-DQ genotypes and the clinical features in our CD pediatric patients. Although, our results suggest an effect of the DQB1-02 allele not only on the level of antibodies to tTG, but possibly also on liver involvement.

Increased Prevalence of Celiac Disease in School-age Children in Italy.

BACKGROUND & AIMS: Celiac disease is one of the most common diseases worldwide, with an apparent trend of increasing prevalence. We investigated the prevalence of celiac disease in children in Italy in 2015-2016 and compared that with data from 25 years ago. METHODS: We screened 4570 children (5-11 years old, 80.1% of the eligible population) from metropolitan areas of Ancona and Verona for HLA genes associated with increased risk of celiac disease, and for total serum levels of IgA and IgA class anti-tissue transglutaminase in HLA positives. Diagnoses of celiac disease were confirmed by detection of anti-endomysial antibody and analysis of intestinal biopsies. The prevalence of celiac autoimmunity and celiac disease were calculated and compared with values from the same geographical area during the years 1993-1995, after adjustment for the different diagnostic algorithm. RESULTS: We identified 1960 children with celiac disease-associated haplotypes (43% of children screened; 95% CI, 40.8%-45.2%). The prevalence of celiac disease autoimmunity in the HLA-positive subjects was 96/1706 (5.62%; 95% CI, 4.53%-6.71%) and 54 of these children satisfied the diagnostic criteria for celiac disease. In the eligible population there were other 23 known cases of celiac disease. The overall estimated prevalence of celiac disease was 1.58% (95% CI, 1.26%-1.90%); this value is significantly higher than the 1993-1995 adjusted prevalence (0.88%; 95% CI, 0.74%-1.02%). CONCLUSIONS: We found the prevalence of celiac disease in children in Italy to be greater than 1.5%; this value has increased significantly over the past 25 years. Studies are needed to determine the causes of this large increase.

Interpretation and implementation of the revised European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines on pediatric celiac disease amongst consultant general pediatricians in Southwest of England.

BACKGROUND: Celiac disease (CD) is a lifelong condition with significant morbidity and requires an accurate diagnosis. Guidelines for pediatric CD were revised by the European and British Societies of Paediatric Gastroenterology Hepatology and Nutrition in 2012 and 2013, respectively. New recommendations introduced non-biopsy pathway (NBP) of diagnosis for a selective group of symptomatic children whose anti-tissue transglutaminase (anti-tTG) antibody titer is greater than ten times upper limit of normal. A clear understanding of the guidelines amongst consultant pediatricians will ensure all children with suspected CD receive a prompt and secure diagnosis. The aim of this study was to establish the interpretation and implementation of the revised guideline for CD amongst consultant general pediatricians in Southwest England (SWE) during the study period. METHODS: Telephone/email survey was conducted amongst consultant general pediatricians (n ≈ 140) working in 12 secondary care hospitals across SWE. The survey included eight questions incorporating three main themes: understanding of diagnostic pathway particularly for non-biopsy diagnosis, awareness of laboratory tests involved, and variations in practice in relation to the revised guidelines. RESULTS: Responses were available from 101/140 (72%). One hundred respondents were aware of the revised guidelines for diagnosing CD. However, only 17 respondents stated all the criteria of the guideline required for diagnosis by NBP, with further 17 seeking immediate advice from a specialist. Forty-four listed both the criteria for HLA-DQ2/DQ8 testing applicable to pediatricians. Forty-nine out of 100 pediatricians would commence gluten-free diet only after all the results were available. Thirty-three pediatricians also considered asymptomatic children with high anti-tTG titer eligible for diagnosis of CD by NBP. CONCLUSIONS: There is a need for improved understanding of revised CD guidelines amongst consultant general pediatricians especially while using the NBP and requesting HLA-DQ2/DQ8 testing.

Role of Human Leukocyte Antigens (HLA) in Autoimmune Diseases.

The aim of this review is to provide a brief overview of the role and current clinical relevance of HLA-B27 in spondyloarthritis and HLA-B51 in Behcet's disease as well as HLA-DQ2/DQ8 in celiac disease and HLA-DRB1 in rheumatoid arthritis and to discuss possible future implications.

Celiac antibodies in children with type 1 diabetes - A diagnostic validation study.

INTRODUCTION: Autoimmune diseases, such as celiac disease (CD) and diabetes mellitus type 1, tend to co-occur within the same patient. The prevalence of CD in diabetic children is higher than in the general population, and is estimated to be 0.6-16.4%. The diagnosis of CD is based on histopathological examination and serological testing, however, these methods are still imperfect and new diagnostic algorithms should be considered. AIM: The aim of the study was to assess the diagnostic value of serological tests detecting antibodies against deamidated gliadin peptide, endomysium, tissue transglutaminase, neo-epitope tissue transglutaminase and to identify HLA-related genetic predisposition to CD in patients with type 1 diabetes mellitus (DM1). METHODS: Autoantibodies were measured in the sera of 392 children suffering from DM1 aged 1-19 years old (mean 11.76 ± 4.14 years old). Additionally, PCR-based assessment of HLA DQ2/DQ8 genotyping was performed. RESULTS: A positive result of at least one serological test was obtained from 81 children (20.66%). The sensitivity and specificity were 76.47% and 91.67% for anti-DGP IgA, 70.59% and 58.33% for IgG anti-DGP, respectively. A positive predictive value was 100% for the anti-TG IgA at cutoff levels of 5 and 10 times higher than upper limit of reference values. HLA DQ2 and/or DQ8 were found in 97.6% of examined children. CONCLUSIONS: Tests based on anti-TG IgA are more accurate for detecting CD in children with type 1 diabetes than anti-DGP IgA. A high percentage of diabetic children carry HLA alleles predisposing to CD, which indicates that genetic screening in this group of patients is not obligated.

Helicobacter pylori infection and occurrence of celiac disease in subjects HLA-DQ2/DQ8 positive: A prospective study.

BACKGROUND: Celiac disease (CD) occurs in subjects positive for HLA-DQ2 and/or DQ8 gene loci at any age following ingestion of gluten-containing food. An increased permeability of the mucosa allows interactions between gliadin macromolecules and genetic factors. It has been observed that Helicobacter pylori has the ability to modulate the integrity of the duodenal epithelium. We aimed to determine whether H. pylori infection may enhance the occurrence of CD in genetically susceptible subjects. MATERIALS AND METHODS: This was a prospective observational study. Patients undergoing upper endoscopy for any reason and positive for HLA-DQ2 and/or DQ8 haplotypes with or without CD were included. H. pylori infection was defined as a positive gastric histopathology and/or 13C-urea breath test. Prevalence of infection was compared between enrolled subjects with and without CD. Multiple logistic regression analysis, adjusting odds ratios for patient age, gender, smoking habit, residency, body mass index, and assumption of nonsteroidal anti-inflammatory drugs (NSAIDs) and proton-pump inhibitors (PPIs) were performed. RESULTS: A total of 397 genetically susceptible individuals (mean age: 37.7 ± 15.3 years; 86% women) were enrolled between October 2014 and October 2017. There were 265 (68%) patients with a diagnosis of CD. Overall, the prevalence of H. pylori infection was 33% and was similar in patients with and without CD (32% vs 36%). Adjustment for all covariates did not reveal any significant association, although adjusted odds ratio (OR) for CD was higher in female (OR = 1.302), in patients H. pylori positive (OR = 1.277), followed by use of NSAIDs (OR = 1.126), respectively. The use of PPIs appeared to be mildly protective against CD (OR = 0.644). CONCLUSION: Our study did not reveal any significant relationship between H. pylori and CD risk, even taking into account other confounders. More importantly, our findings do not support a "protective" role of H. pylori infection against CD, as previously reported. Therefore, there are no reasons to avoid eradication of H. pylori also in subject genetically susceptible for CD.

Genetics, environment, and asthma associated with celiac disease in the extended family of an affected child. / Genética, ambiente y asma asociados a enfermedad celiaca en la familia extendida de un niño afectado.

INTRODUCTION: Celiac disease (CD) is an autoimmune enteropathy associated with gluten ingestion. In extended families of celiac patients that live in close proximity of one another, shared genetic and environmental factors can predispose them to CD. AIM: The aim of this study was to provide evidence about the genetic and environmental factors involved in the development of CD in the extended family of a pediatric patient. METHODS: The medical history, environmental conditions, and participant weight, height, and peripheral blood samples were evaluated. The HLA-DQ2/DQ8 haplotypes were genotyped through qPCR testing and the IgA anti-gliadin and anti-transglutaminase antibodies were quantified using the ELISA test. RESULTS: Twelve close-living maternal relatives of the index case participated in the study. Eight of them presented with the HLA-DQ2 haplotype, inherited from the grandfather, and 7/12 and 9/12 were positive for IgA anti-gliadin and IgA anti-transglutaminase antibodies, respectively. The main intestinal symptoms stated by the participants were abdominal bloating, excess flatulence, constipation, and gastroesophageal reflux. The most frequent extra-intestinal symptoms were fatigue, stress, and anxiety. In addition, 6/13 participants had bronchial asthma. CONCLUSION: The extended family living in close proximity of one another shared a genetic predisposition, environmental conditions, and asthma, which could have predisposed them to celiac disease.

Limited role of HLA DQ2/8 genotyping in diagnosing coeliac disease.

The European guidelines for diagnosing coeliac disease in children were revised in 2012. These recommend that in symptomatic children, a diagnosis of coeliac disease can be made without small-bowel biopsies provided their anti-tissue transglutaminase (anti-tTG) titre is >10 times of upper-limit-of-normal (>10×ULN) and anti-endomysial antibody is positive. In order to firm up the diagnosis in these children with very high anti-tTG titre, HLA-DQ2/DQ8 should be checked and be positive. Approximately 25-40% of white Caucasian population has HLA-DQ2/DQ8 haplotype. However, only 0.1-1% of the population will develop coeliac disease. Therefore, HLA-DQ2/DQ8 testing must not be done to 'screen' or 'diagnose' children with coeliac disease. Its use by paediatricians should be limited to children with anti-tTG>10×ULN, where the diagnosis of coeliac disease is being made on serology alone. A review of case referrals made to a tertiary paediatric gastroenterology centre in Southwest England demonstrated that HLA-DQ2/DQ8 testing is being requested inappropriately both in primary and secondary care suggesting a poor understanding of its role in diagnosis of coeliac disease. This article aims to clarify the role of HLA-DQ2/DQ8 testing for clinicians working in non-specialist settings.

A population-wide applicable HLA-DQ2 and DQ8 genotyping using DNA from dried blood spots and duplex allele-specific qPCR amplification.

Genotyping of HLA-DQ2 and DQ8 haplotypes is important for diagnosis or for screening of early risk detection of celiac disease or type 1 diabetes. Usually, venous blood DNA extraction and expensive and time consuming amplification are used, that hinder population-wide studies. We assayed a friendly HLA-DQ2 and DQ8 genotyping procedure using a combination of DNA from dried blood spot (DBS) and duplex allele-specific qPCR amplification using SYBR Green. DNA was extracted using home-made buffers and compared to an extraction commercial kit. Duplex reactions by qPCR were designed using each Tm allele amplicon for reference samples (positive HLA-DQ2 or DQ8) with allele-specific primers. DBS samples from 558 children (7.99 ± 2.47 y) were collected. The DNA final yield obtained by the home-made extractive procedure was higher than from the commercial kit (1.11 ± 0.56 vs 0.23 ± 0.14 µg), while the quality was similar for both DNA samples. There was concordance in the amplification profiles for DNA samples obtained with both methods. All of four alleles from DQ2 and DQ8 haplotypes were accurately identified in duplex reactions. By using DBS samples and DNA extraction home-made procedure, the costs were reduced by 60%. The whole procedure is cost-effective for HLA-DQ2 and DQ8 genotyping.

[Adult Celiac Disease]. / Zöliakie beim Erwachsenen.

Celiac disease is an immune-mediated enteropathy in genetically predisposed individuals, triggered by gluten ingestion. Clinical manifestations include intestinal and extraintestinal symptoms. Affected individuals may also be completely asymptomatic. Nevertheless, an early diagnosis is essential in order to prevent long-term complications. Diagnostic approach involves serologic testing for tissue transglutaminase antibodies followed by duodenal biopsy in case of seropositivity. Until now, the only available treatment consists of a strict glute-free diet. Newer therapeutic strategies are currently being evaluated in clinical trials.

Cross-sectional study of coeliac autoimmunity in a population of Vietnamese children.

OBJECTIVE: The prevalence of coeliac disease (CD) in Vietnam is unknown. To fill this void, we assessed the prevalence of serological markers of CD autoimmunity in a population of children in Hanoi. SETTING: The outpatient blood drawing laboratory of the largest paediatric hospital in North Vietnam was used for the study, which was part of an international project of collaboration between Italy and Vietnam. PARTICIPANTS: Children having blood drawn for any reason were included. Exclusion criteria were age younger than 2 years, acquired or congenital immune deficiency and inadequate sample. A total of 1961 children (96%) were enrolled (838 females, 1123 males, median age 5.3 years). OUTCOMES: Primary outcome was the prevalence of positive autoimmunity to both IgA antitransglutaminase antibodies (anti-tTG) assessed with an ELISA test and antiendomysial antibodies (EMA). Secondary outcome was the prevalence of CD predisposing human leucocyte antigens (HLA) (HLA DQ2/8) in the positive children and in a random group of samples negative for IgA anti-tTG. RESULTS: The IgA anti-tTG test was positive in 21/1961 (1%; 95% CI 0.61% to 1.53%); however, EMA antibodies were negative in all. HLA DQ2/8 was present in 7/21 (33%; 95% CI 14.5% to 56.9%) of the anti-tTG-positive children and in 72/275 (26%; 95% CI 21% to 32%) of those who were negative. CONCLUSIONS: Coeliac autoimmunity is rare in Vietnam, although prevalence of HLA DQ2/8 is similar to that of other countries. We hypothesise that the scarce exposure to gluten could be responsible for these findings.

The role of nurses and dietitians in managing paediatric coeliac disease.

Coeliac disease (CD) is an immune-mediated genetic condition elicited by the ingestion of gluten, leading to proximal small bowel enteropathy. It affects around 1% of the population, although only a small proportion of cases are actually diagnosed. It is a multisystem disorder presenting with both gastrointestinal and extra-intestinal manifestations such as diarrhoea, abdominal pain, constipation, vomiting, iron deficiency anaemia, faltering growth, dental enamel defects, short stature, liver disease, arthropathy and recurrent aphthous ulcers. Nurses, working in different clinical settings, are best placed for early recognition and diagnosis of CD in children. Suspicion of CD should lead to immunoglobulin A (IgA)-based anti-tissue transglutaminase antibody screening tests and a diagnosis confirmed by an intestinal biopsy. Modification of European (ESPGHAN) guidelines now enables CD to be diagnosed without a small-bowel biopsy in a select group of symptomatic children. A gluten-free diet should preferably be started by paediatric dietitians. Strict adherence to a gluten-free diet is essential to maintain good health and to prevent long-term complications. A case study demonstrating some of the challenges that may be faced in children with CD in clinical practice is described. Specialist nurse-led CD clinics are gaining popularity and have been found to be equally effective in providing continuity of quality care.

Human leukocyte antigen (HLA) DQ2/DQ8 prevalence in recurrent pregnancy loss women.

OBJECTIVE: Over the last few years, medical scholars have reported the significant association between recurrent pregnancy loss (RPL) and celiac disease (CD). Various pathogenic mechanisms underlying the pregnancy failure in CD have been suggested: among them the ability of anti-transglutaminase antibodies to impair the trophoblast invasiveness and endometrial endothelial cells differentiation and disrupt early placentation. CD shows a complex non-Mendelian pattern of inheritance, involving major histocompatibility complex (MHC) genes. The strongest effects are mapped to the classical human leukocyte antigen (HLA)-DQA1 and HLA-DQB1 genes. Specifically, the common haplotypes DQ2.5, DQ2.2, and DQ8 have been shown to increase CD risk by six-fold on average. MHC region contains genes with immunological functions and is responsible for the strongest association signals observed in most immune-mediated diseases. The aim of our study was to investigate the prevalence of the HLA-DQ2/DQ8 haplotypes in RPL, outside of CD. METHODS: The study population included women with history of RPL (≥3 spontaneous pregnancy losses) and women with at least two previous uncomplicated term pregnancies (control group, CTR). All women gave their informed consent to use their data for research purposes. RESULTS: 97 RPL women and 55 CTR were considered in the study. Mean age of the RPL sample was 37.7 (standard deviation, SD, 3.0; min 27; max 39). Mean age of the control group was 35.6 (SD 3.0; min 26years; m, max 38). A significantly increased prevalence of HLA-DQ2/DQ8 haplotype positivity was found in RPL population compared to control women (52.6% vs 23.6%; p<0.01). CONCLUSIONS: Our observations show for the first time a higher proportion of individuals HLA DQ2/DQ8 positive in women with RPL as compared to controls (and to general population estimates). Further studies are needed to better understand (i) the possible pathogenic mechanism to this observation; (ii) the clinical and therapeutic implications of our observation in order to provide a new approach to RPL couples.

The prevalence of celiac disease in patients with irritable bowel syndrome and its subtypes.

INTRODUCTION: Irritable bowel syndrome (IBS) and celiac disease (CD) share some gastrointestinal symptoms. Celiac disease should be considered in a differential diagnosis of IBS. AIM: To estimate the prevalence of predispositions to CD in patients with IBS and its subtypes. MATERIAL AND METHODS: The study included 48 patients (40 women, 8 men; average age: 41.1 ±14.6 years) with IBS, and a control group: 20 healthy volunteers. All participants completed a questionnaire on their current gastrointestinal symptoms and had a blood sample taken to determine the HLA-DQ2/DQ8 antigens and serum concentration of anti-tTG IgA and anti-DGP IgA and IgG. RESULTS: The presence of HLA-DQ2 or DQ8 was found in 50% of patients (n = 24) with IBS. In the control group the presence of HLA-DQ2 was found in 4 (20%) patients and nobody had HLA-DQ8. Increased levels of anti-tTG IgA were found in 5 (10.42%) patients with IBS, anti-DGP in 4 (8.33%), and anti-DGP IgG in 3 (6.25%). In the control group positive test result for anti-tTG was found in 2 (10%) patients; nobody had elevated anti-DGP IgA or IgG. A concomitant positive result of genetic testing and any elevated serum antibodies specific to CD was found in 12.5% of IBS patients (n = 6) and in none of the control group. CONCLUSIONS: Patients with IBS, regardless of the subtype, significantly more often than healthy controls have the predisposing genetic factors (HLA-DQ2/DQ8) underlying the development of CD.

Celiac disease: advances in diagnosis.

Celiac disease (CD) is characterized by small intestinal damage, which is mediated by a gluten-driven inflammatory response. Establishing a robust diagnosis is critical for improved quality of life and prevention of co-morbidities, although treatment is associated with a substantial life-long burden of care for patients and families. Unfortunately, CD remains a challenging diagnosis. As awareness of the disease increases, more diagnoses of CD are being made by primary care physicians. In fact, many patients may not present to a gastroenterologist because their symptoms are not clearly linked to a gastrointestinal pathology. Also, many patients are starting a gluten-free diet without prior testing, a circumstance that leads to even more confusion. Lastly, the number of serologic and genetic tests, and the role of endoscopy, can be confusing. The purpose of this review is to examine diagnostic testing strategies, focusing on published guidelines, for the evaluation of patients with suspected CD.