Investigating associations between HLA DQA1 ~ DQB1 haplotypes, H. pylori infection, metaplasia, and anti-CagA IgA seropositivity in a Turkish gastritis cohort

Colakogullari, Mukaddes; Karatas, Lokman; Tatar, Zeynep

doi:10.1007/s00251-023-01325-5

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“…HLA DRB1*11:04 was co-inherited with HLA DQA1*05:05-DQB1*03:01 haplotype in 2.5% frequency among Americans of European descent [ 44 ]. The DRB1*11:04 allele was found to be significantly correlated with both DQA1*05:05 and DQB1*03:01 alleles as well as with the DQA1*05:05~DQB1*03:01 haplotype in our study population (unpublished data) [ 45 ]. However, since these patients are diagnosed as having gastritis, all these alleles might be enriched in our cohort.…”

Section: Discussionmentioning

confidence: 91%

Investigating Associations between HLA-DR Genotype, H. pylori Infection, and Anti-CagA IgA Seropositivity in a Turkish Gastritis Cohort

Karataş,

Tatar,

James

et al. 2024

Genes

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Helicobacter pylori (H. pylori) is associated with gastric inflammation and mucosal antibodies against its cytotoxin-associated gene A (CagA) are protective. Vaccine-elicited immunity against H. pylori requires MHC class II expression, indicating that CD4+ T cells are protective. We hypothesized that the HLA-DR genotypes in human populations include protective alleles that more effectively bind immunogenic CagA peptide fragments and susceptible alleles with an impaired capacity to present CagA peptides. We recruited patients (n = 170) admitted for gastroendoscopy procedures and performed high-resolution HLA-DRB1 typing. Serum anti-CagA IgA levels were analyzed by ELISA (23.2% positive) and H. pylori classified as positive or negative in gastric mucosal tissue slides (72.9% positive). Pearson Chi-square analysis revealed that H. pylori infection was significantly increased in DRB1*11:04-positive individuals (p = 0.027). Anti-CagA IgA was significantly decreased in DRB1*11:04 positive individuals (p = 0.041). In contrast, anti-CagA IgA was significantly increased in DRB1*03:01 positive individuals (p = 0.030). For these HLA-DRB1 alleles of interest, we utilized two in silico prediction methods to compare their capacity to present CagA peptides. Both methods predicted increased numbers of peptides for DRB1*03:01 than DRB1*11:04. In addition, both alleles preferred distinctively different CagA 15mer peptide sequences for high affinity binding. These observations suggest that DRB1*11:04 is a susceptible genotype with impaired CagA immunity, whereas DRB1*03:01 is a protective genotype that promotes enhanced CagA immunity.

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Section: Discussionmentioning

confidence: 91%