Gluten-dependent enteropathy and atypical human leukocyte antigen alleles

Harmon, Gregory S.; Lebeck, Lauralynn K.; Weidner, Noel

doi:10.1016/j.humpath.2010.10.010

Cited by 14 publications

(17 citation statements)

References 28 publications

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“…However, other reports describe patients with CD who lack both HLA-DQ2.5 and -DQ8, making the validity of this strong negative predictive value questionable (13)(14)(15)(16)(17)(18) . Previous studies already showed that a great proportion of DQ2.5 and DQ8 negative CD patients were positives for the DQ2.2 variant (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) concluding that DQ2.2 should be considered as a risk variant for celiac disease.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies already showed that a great proportion of DQ2.5 and DQ8 negative CD patients were positives for the DQ2.2 variant (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) concluding that DQ2.2 should be considered as a risk variant for celiac disease. Other studies also gave details on the probable molecular role of the heterodimer coded by this variants (18,19) . However, we found no significant difference between celiac and non-celiac children, suggesting that this variant is not relevant for the population under analysis.…”

Section: Discussionmentioning

confidence: 99%

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Prevalence of Celiac Disease Predisposing Genotypes, Including HLA-DQ2.2 Variant, in Brazilian Children

Selleski

Almeida

et al. 2018

Arq. Gastroenterol.

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-Background -Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Almost all celiac patients carry immune recognition genes coding for HLA-DQ2.5 and DQ8 heterodimers. Over the last few years, great importance has been given to HLA-DQ2.2 as probable predisposing variant, although controversies still exist regarding its relevance. Objective -The aim of our study was to determine the possible existence of an association between HLA-DQ2.2 and celiac disease in Brazilian children by analyzing the prevalence of the predisposing variants for celiac disease in a representative group of children of a population in which this determination is still missing. Methods -HLA-DQ typing was performed in samples from a group of celiac (n=100) and non-celiac children (n=110). All samples were tested for the presence of the following variants: DQA1*05-DQB1*02 (DQ2.5), DQA1*03-DQB1*03:02 (DQ8) and DQA1*02:01-DQB1*02:02 (DQ2.2). Fisher`s exact test was used for statistical analysis. Results -In the group of 100 celiac children, 78 (78%) were positive for DQ2, 13 (13 %) were DQ2/DQ8 and 6 (6%) were DQ8 positives. The HLA-DQ pattern in the 110 non-celiac children was as follows: positive for DQ2 in 33 (29.9%) samples, in 2 (1.8 %) was positive for DQ2/DQ8 and in 15 (13.6%) was positive for DQ8. We found significant differences between the distribution of some but not all of the analyzed alleles when comparing celiac and non-celiac children. Conclusion -The genotyping of celiac disease HLA-DQ predisposing alleles showed similarities with HLA-DQ patterns found in both European and non-European populations, which may be a reflection of the miscegenation, which gave origin to the current Brazilian population. No significant association was found between DQ2.2 variant and celiac disease in the studied population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prevalence of Celiac Disease Predisposing Genotypes, Including HLA-DQ2.2 Variant, in Brazilian Children

Selleski

Almeida

et al. 2018

Arq. Gastroenterol.

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“…DQ2.5 homozygosity confers a fivefold increased risk of CD, compared to heterozygotes, with intermediate risk for DQ2.5/DQ8 compound heterozygotes. The closely related alleles, DQ2.2 (DQA*0201/DQB*02) and DQ0602 (DQA1*0102/DQB1*0602), carry a very low risk for CD (53). Interestingly, latent CD (i.e., positive serology without clinical disease) tends to be associated with low-risk DQ genotypes (54).…”

Section: Celiac Diseasementioning

confidence: 99%

On the perils of poor editing: regulation of peptide loading by HLA-DQ and H2-A molecules associated with celiac disease and type 1 diabetes

Busch

Riva

Hadjinicolaou

et al. 2012

Expert Rev. Mol. Med.

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This review discusses mechanisms that link allelic variants of MHC class II molecules (MHCII) to immune pathology. We focus on HLA-DQ (DQ) alleles associated with celiac disease (CD) and type 1 diabetes (T1D) and the role of the murine DQ-like allele, H2-Ag7 (Ag7), in murine T1D. MHCII molecules bind peptides, and alleles vary in their peptide-binding specificity. Disease-associated alleles permit binding of disease-inducing peptides, such as gluten-derived, Glu-/Pro-rich gliadin peptides in CD and peptides from islet autoantigens, including insulin, in T1D. In addition, the CD-associated DQ2.5 and DQ8 alleles are unusual in their interactions with factors that regulate their peptide loading, invariant chain (Ii) and HLA-DM (DM). The same alleles, as well as other T1D DQ risk alleles (and Ag7) share nonpolar residues in place of Asp at β57 and prefer peptides that place acidic side chains in a pocket in the MHCII groove (P9). Antigen-presenting cells from T1D-susceptible mice and humans retain CLIP due to poor DM editing, although underlying mechanisms differ between species. We propose that these effects on peptide presentation make key contributions to CD and T1D pathogenesis.

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“…They will also help us characterize clearly as CD sufferers the small number of patients who are both DQ2 and DQ8 negative, as observed in 8.82% of the adult patients in our series and which has been described to occur in 6% of the European population [50]. In fact, a recent study evaluating the frequency of DQ2 and DQ8 alleles in 127 consecutive cases of adult-onset CD found that all patients with atypical HLA responded to a gluten-free diet [51]. Most DQ2 and DQ8 negative patients in our series encoded half of the DQ2 heterodimer as the low-risk haplotype DQ2.02 (DQA1*02 and DQB1*02) or as DQA*05, as recently described in case series from Europe [50] and the USA [51] for patients who responded to a GFD.…”

Section: Discussionmentioning

confidence: 57%

Coeliac Disease in the 21st Century: No Longer “Kids’ Stuff”

Lucendo

García-Manzanares

Arias³

et al. 2011

Gastroenterol Res

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BackgroundWe aimed to determine if Coeliac disease (CD) can be still be considered a predominantly paediatric disorder, in spite of the increased incidence of adult-onset CD reported in recent years.MethodsAn observational, descriptive, and retrospective study was developed at two Spanish hospitals. Data was collected and analyzed from all paediatric and adult patients newly diagnosed with CD throughout the year 2010. CD diagnoses were based on a concordant clinical history, serology, HLA-DQ compatibility, the presence of mucosal lesions in duodenal biopsies with gluten dependence of symptoms, and histological lesions.ResultsA total of 79 patients were diagnosed with CD throughout 2010, of which 68 (86.1%) were adults. Classic symptoms (diarrhoea and iron-deficiency anaemia) were more frequent in children (90.9%), being present in only 54.4% of adults (p = 0.02). Adult patients showed, mainly, abdominal pain, dyspepsia, and GERD-related symptoms. Villous atrophy (Marsh III) was present in 63.7% of children, but only in 19.1% of adults (p = 0.004). Positive tTGA was present in 81.8% of the children and only in 19.1% of the adults (p = 0.004). Haemoglobin levels were significantly lower in children (p = 0.025), but no differences were observed in iron and ferritin blood levels.ConclusionsOur study shows that adult-onset CD was the predominant presentation in two hospitals in Spain in the year 2010. Therefore, CD can no longer be considered a predominantly paediatric disorder. Marsh I and negative tTGA titters are characteristic in most of adults. New diagnostic algorithms are needed to improve correct diagnosis of CD in adults.

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Gluten-dependent enteropathy and atypical human leukocyte antigen alleles

Cited by 14 publications

References 28 publications

Prevalence of Celiac Disease Predisposing Genotypes, Including HLA-DQ2.2 Variant, in Brazilian Children

Prevalence of Celiac Disease Predisposing Genotypes, Including HLA-DQ2.2 Variant, in Brazilian Children

On the perils of poor editing: regulation of peptide loading by HLA-DQ and H2-A molecules associated with celiac disease and type 1 diabetes

Coeliac Disease in the 21st Century: No Longer “Kids’ Stuff”

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