Modeling Peptide-Protein Interactions by a Logo-Based Method: Application in Peptide-HLA Binding Predictions.

Peptide-protein interactions form a cornerstone in molecular biology, governing cellular signaling, structure, and enzymatic activities in living organisms. Improving computational models and experimental techniques to describe and predict these interactions remains an ongoing area of research. Here, we present a computational method for peptide-protein interactions' description and prediction based on leveraged amino acid frequencies within specific binding cores. Utilizing normalized frequencies, we construct quantitative matrices (QMs), termed 'logo models' derived from sequence logos. The method was developed to predict peptide binding to HLA-DQ2.5 and HLA-DQ8.1 proteins associated with susceptibility to celiac disease. The models were validated by more than 17,000 peptides demonstrating their efficacy in discriminating between binding and non-binding peptides. The logo method could be applied to diverse peptide-protein interactions, offering a versatile tool for predictive analysis in molecular binding studies.

Celiac disease prevalence and predisposing-HLA in a cohort of 93 Williams-Beuren syndrome patients.

Williams-Beuren syndrome is considered to be at increased risk for celiac disease, as for recent literature data and celiac disease guidelines, despite pathogenic mechanisms are still unclear. Our study analyzed the prevalence of autoimmune disorders, HLA DQ2 and/or DQ8 haplotypes, of transglutaminase antibodies and of diagnosis of celiac disease in a cohort of 93 Williams-Beuren syndrome's patients (mean age 21.26 years). Our study showed an increased prevalence of celiac disease equal to 10.8% (10/93 patients). We did not find a significant different frequency of predisposing HLA in subjects with Williams-Beuren syndrome compared to literature data in the general population (49.5% vs. 42.9%, with p > .1), nor a susceptibility to autoimmunity. This suggests that the increased prevalence of celiac disease in Williams-Beuren syndrome cannot be ascribed to HLA haplotype and may be related to other factors that still need to be identified in these patients.

Meta-Analysis and Systematic Review of HLA DQ2/DQ8 in Adults with Celiac Disease.

Although people with human leukocyte antigens (HLA) DQ2 and/or DQ8 are more likely to develop celiac disease (CD), the condition cannot be fully explained by this genetic predisposition alone. Multiple, as yet unidentified, factors contribute to the genesis of CD, including genetics, the environment, and the immune system. In order to provide insight into a prospective possibility and an expanded screening technique, we aim to undertake a comprehensive and meta-analytical study of the assessment and distribution of HLA class II (HLA-DQ2/DQ8) in adult CD patients. A systematic review was conducted using an electronic search of databases (PubMed, Google Scholar, Embase, and Direct Science) from January 2004 to February 2022. DQ2/DQ2 homozygotes have the highest risk of developing CD. DQ2/DQ8 typing is an effective test to exclude CD from the differential diagnosis of a patient with CD symptoms. Although other non-HLA genes have been associated with CD, they are rarely considered at diagnosis because they account for only a small proportion of the heritability of CD. This finding, together with the information gathered previously, may be useful in considering widely available and economically feasible screening options for celiac disease in young people.

Assessment of Novel Proteins Triggering Celiac Disease via Docking-Based Approach.

Human leukocyte antigens (HLAs) are pivotal in antigen processing, presenting to CD4+ T cells, and are linked to autoimmune disease susceptibility. In celiac disease, HLA-DQ2.5 and HLA-DQ8.1 bind gluten peptides on APCs, some recognized by CD4+ T cells, prompting inflammation and tissue damage. While extensively studied experimentally, these alleles lack comprehensive in silico analysis. To explore peptide-HLA preferences, we used molecular docking on peptide libraries, deriving quantitative matrices (QMs) for evaluating amino acids at nine-residue peptide binding cores. Our findings tie specific residue preferences to peptide backbone conformations. Validating QMs on known binders and non-binders showed strong predictive power (89-94% accuracy). These QMs excel in screening protein libraries, even whole proteomes, notably reducing time and costs for celiac disease risk assessment in novel proteins. This computational approach aligns with European Food Safety Authority guidance, promising efficient screening for potential celiac disease triggers.

Characterization of T-cell receptor transgenic mice recognizing immunodominant HLA-DQ2.5-restricted gluten epitopes.

We created a TCR transgenic mouse with CD4+ T cells recognizing the immunodominant DQ2.5-glia-ω2 gluten epitope. We show that these cells respond to deamidated gluten feed in vivo and compare them to previously published α2- and γ1-specific mice. These mice may help enlighten key aspects of celiac disease pathogenesis.

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.

Update 2020: nomenclature and listing of celiac disease-relevant gluten epitopes recognized by CD4+ T cells.

Celiac disease is caused by an abnormal intestinal T cell response to cereal gluten proteins. The disease has a strong human leukocyte antigen (HLA) association, and CD4+ T cells recognizing gluten epitopes presented by disease-associated HLA-DQ allotypes are considered to be drivers of the disease. This paper provides an update of the currently known HLA-DQ restricted gluten T cell epitopes with their names and sequences.

Association Between Celiac Disease and Cancer.

Celiac disease (CD) is a chronic enteropathy that develops in genetically susceptible individuals after the ingestion of gluten. There has been a substantial increase in CD prevalence in the last 50 years, and it is now estimated that this disease affects approximately 1% of the population in the Western world. In the large majority of cases, CD is a benign disease, characterized by the complete resolution of symptoms and a normal life expectancy after the onset of a gluten-free diet (GFD). However, failure to adhere to a strict GFD bears the risk of adverse events and increases mortality. A considerable number of studies have considered the possible association between CD and neoplasms. In particular, an increased risk of malignancies, such as cancers of the gastrointestinal tract and intestinal lymphomas, has been reported. In this review, we summarize and discuss the current evidence on the possible association between CD and cancer.

Proinsulin peptide promotes autoimmune diabetes in a novel HLA-DR3-DQ2-transgenic murine model of spontaneous disease.

AIMS/HYPOTHESIS: The molecular basis for the pathological impact of specific HLA molecules on autoimmune diseases such as type 1 diabetes remains unclear. Recent natural history studies in children have indicated a link between specific HLA genotypes and the first antigenic target against which immune responses develop. We set out to examine this link in vivo by exploring the diabetogenicity of islet antigens on the background of a common diabetes-associated HLA haplotype. METHODS: We generated a novel HLA-transgenic mouse model that expresses high-risk genes for type 1 diabetes (DRB1*03:01-DQA1*05:01-DQB1*02:01) as well as human CD80 under the rat insulin promoter and human CD4, on a C57BL/6 background. Adjuvanted antigen priming was used to reveal the diabetogenicity of candidate antigens and peptides. RESULTS: HLA-DR3-DQ2+huCD4+IA/IE-/-RIP.B7.1+ mice spontaneously developed autoimmune diabetes (incidence 46% by 35 weeks of age), accompanied by numerous hallmarks of human type 1 diabetes (autoantibodies against GAD65 and proinsulin; pancreatic islet infiltration by CD4+, CD8+ B220+, CD11b+ and CD11c+ immune cells). Disease was markedly accelerated and had deeper penetrance after adjuvanted antigen priming with proinsulin (mean onset 11 weeks and incidence 100% by 20 weeks post challenge). Moreover, the diabetogenic effect of proinsulin located to the 15-residue B29-C11 region. CONCLUSIONS/INTERPRETATION: Our study identifies a proinsulin-derived peptide region that is highly diabetogenic on the HLA-DR3-DQ2 background using an in vivo model. This approach and the peptide region identified may have wider implications for future studies of human type 1 diabetes.

Is the double gene dose of DQ2.5 or DQ2.5/DQ2.2 an involved factor in the clinical features of celiac disease?

Objectives: Celiac disease (CD) is barely known if the quantitative effect of DQB1*02 (DQ2) double dose in antigen presentation to T-cells has translation into the clinic. For this, we have conducted a case-control study in a cohort of two hundred and nineteen patients with CD. Material and methods: For the control group, individuals were enrolled with single dose of DQ2, carrying DQ2.5 heterodimers in heterozygous state (n = 109). The cases with CD were diving into three groups: cases with overall DQ2 double dose (n = 110), DQ2.5 homozygous (n = 33) and DQ2.5/DQ2.2 heterozygous (n = 77). Prevalence and associations of demographic, laboratory, histological and clinical characteristics between the control group and cases were studied. Results: No differences were found for the total of 16 variables analyzed between the control group and overall DQ2 double dose as well as DQ2.5 homozygous cases. In contrast to DQ2.5/DQ2.2, heterozygous cases presented a protection factor for developing allergy to airway allergens regarding the control group (OR = 0.210, p = .019). Conclusions: To date, this negative association has not been described. Further studies will be necessary to elucidate the implication of this protection factor in CD. Since, until now the association between CD and allergic diseases has been poorly studied.

Structural insights on P31-43, a gliadin peptide able to promote an innate but not an adaptive response in celiac disease.

Inflammation of intestinal tissue in patients affected by celiac disease (CD) originates from the adaptive and innate immune responses elicited by the undigested gliadin fragments through molecular mechanisms not yet completely described. Undigested A-gliadin peptide P31-43 is central to CD pathogenesis, entering enterocytes in vesicular compartments by endocytosis and inducing an innate immune response in CD intestinal mucosa. This study focused on the reasons why P31-43 does not behave as adaptive immunogenic agent. Once obtained by NMR analysis, the three-dimensional model of P31-43 was used to implement a series of in silico experiments aimed to explore the ability of the peptide to interact with HLA-DQ2 and the corresponding receptor onto T cells. Our results show that P31-43 is a poor ligand for DQ2 and/or T-cell receptor. This study was also aimed to investigate, from a structural point of view, the previous experimental findings by which P31-43 is able to enhance the phosphorylation level of the protein ERK2, while some P31-43 Ala-mutants decrease or totally inhibit that process. The molecular models of P31-43, P31-43 P36A, and F37A mutants were used for in silico docking experiments onto the ERK2 structure. The experiments support the hypothesis that P31-43 F37A works as an ERK2 phosphorylation inhibitor because it binds to the ERK2 phosphorylation site. This study reports on the structural properties of so far never NMR characterized gliadin peptides relevant in CD and explores details about their mechanisms of action.

HLA-DQ2 homozygosis increases tTGA levels at diagnosis but does not influence the clinical phenotype of coeliac disease: A multicentre study.

BACKGROUND AND PURPOSE: Magnitude of gluten-specific T-cell responses in coeliac disease (CD) might be dependent on HLA-DQ2 gene dose. We aimed to investigate the effects of HLA-DQB1*02 allele dose on clinical outcomes. METHODS: We reviewed the charts of all coeliac patients attending to three Hungarian university clinics after 1997 and included those patients, who (a) were diagnosed with CD, (b) underwent high-resolution HLA typing and (c) were ≥18 years at the time of data collection. HLA typing was performed to determine DQB1*02 allele dose. Patients were divided into risk groups by DQB1*02 allele dose, as follows: high-, intermediate- and low-risk groups corresponded to a double, single and zero doses, respectively. We used ANOVA and Pearson's chi-squared test to explore association between HLA risk and clinical variables. RESULTS: A total of 727 coeliac patients attended the clinics but only 105 (14.4%) patients were eligible for inclusion. High, intermediate and low HLA risk patients comprised 35.3%, 52.3% and 12.3% of the study population, respectively. Double dose of HLA-DQB1*02 was more frequent in patient with high tTGA level (>10 times the upper limit of normal; p = 0.045). Gene dose was not associated with younger age at diagnosis (p = 0.549), gender (p = 0.739), more severe diagnostic histology (p = 0.318), more frequent classical presentation (p = 0.846), anaemia (p = 0.611), metabolic bone disease (p = 0.374), dermatitis herpetiformis (p = 0.381) and autoimmune diseases (p = 0.837). CONCLUSIONS: Our study shows a significant gene dose effect in terms of tTGA level at diagnosis, but no significant association between HLA-DQB1*02 allele dose and the clinical outcomes in CD.

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.

Risk variation in celiac disease in a population from Southern Spain: evaluating the influence of the DQB1*02:02 allele frequency.

OBJECTIVES: To date, the greatest genetic risk factor known for celiac disease (CD) is the presence of HLA-DQ2 heterodimers, specifically DQ2.5 in state of homozygosis or heterozygosis. DQ2.2 variants are the second most important risk factor when carried trans to DQ2. This study aimed to determine the prevalence and risk genotypes of HLA-DR-DQ. MATERIAL AND METHODS: A total of 196 patients with CD and 206 healthy controls from the Province of Málaga (southern Spain) were included. The corresponding risk gradient in our population was established in accordance with the odds ratios (ORs) found. RESULTS: The heterozygous genotype for DR7-DQ2.2/DR3-DQ2.5 presented the highest risk (OR =6.404, p = .0001) followed by the DR3-DQ2.5 homozygous genotype (OR =4.721, p = .001). An intermediate risk was found for the DQ2.5 heterozygous genotype with no other DQ risk variant (DQ8 or DQ2.2). Similarly, these three genotypes had also an increase in the risk of associated-autoimmune diseases. The DQB1*02:01 allele was the most widely represented among patients with CD respect to the control group (f = 0.479, p = .0001), with the second most common being DQB1*02:02 (f = 0.209, p = .0001). CONCLUSIONS: In addition to the gene dosage effect confirmed in our report, and in contrast with previous studies, we found a raised risk for those patients with DQ2.2 heterodimers in trans configuration to DQ2.5 compared to DQ2.5 homozygous individuals. Therefore, in our population of patients with CD the frequency of DQ2.2 acts as a factor that increases the genetic risk of developing CD.

Long-term response to gluten-free diet as evidence for non-celiac wheat sensitivity in one third of patients with diarrhea-dominant and mixed-type irritable bowel syndrome.

PURPOSE: Irritable bowel syndrome (IBS) is common but therapies are unsatisfactory. Food is often suspected as cause by patients, but diagnostic procedures, apart from allergy testing, are limited. Based on the hypothesis of non-celiac wheat sensitivity (WS) in a subgroup of IBS patients, we tested the long-term response to a gluten-free diet (GFD) and investigated HLA-DQ2 or -DQ8 expression as a diagnostic marker for WS in diarrhea-dominant (IBS-D) and mixed-type IBS (IBS-M). METHODS: The response to a GFD served as reference test for WS and HLA-DQ2/8 expression was determined as index test. Patients were classified as responders if they reported complete or considerable relief of IBS symptoms on at least 75 % of weeks over a 4-month period of gluten-free diet. Established questionnaires (IBS-Quality of Life (IBS-QoL), IBS Symptom Severity Scale (IBS-SSS), European Quality of Life-5 Dimensions (EQ-5D)) were used for secondary outcome measures. RESULTS: Thirty-five patients finished the study. Of these, 12 (34 %) were responders and classified as having WS (95 % CI 21-51 %). HLA-DQ2/8 expression had a specificity of 52 % (95 % CI 33-71 %) and sensitivity of 25 % (95 % CI 8-54 %) for WS. Responders showed improvement in quality of life and symptom scores. At 1-year follow-up, all responders and 55 % of non-responders were still on GFD and reported symptom relief. CONCLUSION: Using strict criteria as recommended for IBS studies, about one third of patients with IBS-D or IBS-M are wheat sensitive, with a similar proportion in both IBS types. Expression of HLA-DQ2/8 is not useful as diagnostic marker for WS. Long-term adherence to a GFD is high and can sustain symptomatic improvement.

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.

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.

HLA-DQ genetic risk gradient for type 1 diabetes and celiac disease in northwestern Mexico.

BACKGROUND: Type 1 diabetes (T1D) and celiac disease (CD) are the 2 most common autoimmune childhood diseases that share their HLA-DQ2 and DQ8 genetic origin. There has currently been an increase in both diseases worldwide. In children from the low-population State of Sonora (15 inhabitants/km(2)) in north-western Mexico, there is no information on their genetic risk or the distribution of the related alleles in the general population. AIMS: To compare the HLA-DQ allele frequency in a representative sample of newborns from Sonora with that of T1D and CD patients to determine the risk gradient, and to identify the presence of celiac autoimmunity in the T1D group. METHODS: The study included 397 Sonoran newborns, with 44 cases of T1D, and 25 CD cases. The CD and T1D cases were clinically diagnosed by specialists at the Hospital Infantil del Estado de Sonora, and the autoantibodies were determined by ELISA. Whole blood was collected, gDNA was extracted, and HLA-DQ2 and DQ8 were typed by PCR-SSP. The risk gradient was calculated by comparing the allele frequencies of the cases with those of the newborns. RESULTS: The Sonoran HLA-DQ risk heterodimer proportion was 16.1% for HLA-DQ2 and 13.6% for HLA-DQ8, with an HLA-DQ2:HLA-DQ8 ratio of 1.2:1. The DQ8/DQ2 genotype represented a 1:14 risk for T1D, whereas the DQ8/DQB1*0201 combination showed a 1:6 risk for CD. The prevalence of CD autoimmunity in T1D children was 7%. CONCLUSION: The Sonoran population has a distinctive HLA-DQ allele distribution due to its ancestry. The HLA-DQ8 combinations with DQ2 or one of its alleles conferred the highest risk for both diseases, and T1D and CD frequently appear together.

Paediatric celiac patients carrying the HLA-DR7-DQ2 and HLA-DR3-DQ2 haplotypes display small clinical differences.

AIM: The aim of this study was to determine the relevance of HLA-DR7-DQ2 typing in a prospective cohort of paediatric coeliac disease patients from Southern Europe. METHODS: This cross-sectional study tested 249 paediatric patients with coeliac disease. HLA-DR3-DQ2 was typed in combination with HLA-DR7-DQ2 to screen for the HLA-DQ2 haplotype. The histological, analytical and clinical characteristics of the subjects were recorded. RESULTS: A total of 91 coeliac patients were diagnosed: 96.7% carried HLA-DQ2 and 4.4% carried HLA-DQ8. In percentage terms, 80.2% of patients carried HLA-DR3-DQ2 and 34.1% carried HLA-DR7-DQ2. We did not find significant differences between HLA-DR7-DQ2 and HLA-DR3-DQ2 paediatric patients with respect to histological damage and clinical characteristics, except for irritability and weight loss. These characteristics were more frequent in HLA-DQ2trans than in HLA-DQ2cis (22.2% vs. 0.0% [p = 0.035] and 55.6% vs. 21.4% [p = 0.017], respectively). Coeliac-specific autoantibody levels were higher in HLA-DQ2cis than one half of HLA-DQ2trans patients (105.5 vs. 19.2 U/mL, p = 0.014). CONCLUSION: Small clinical differences were found between paediatric coeliac patients carrying HLA-DR7-DQ2 and HLA-DR3-DQ2. For a correct screening of HLA-DQ2, at least in our geographical population, the HLA-DR7-DQ2 haplotype should be typed due to its frequency and clinical presentation.