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Investigating associations between HLA DQA1 ~ DQB1 haplotypes, H. pylori infection, metaplasia, and anti-CagA IgA seropositivity in a Turkish gastritis cohort
Immunogenetics ( IF 3.2 ) Pub Date : 2023-11-18 , DOI: 10.1007/s00251-023-01325-5
Mukaddes Colakogullari 1 , Lokman Karatas 1 , Zeynep Tatar 1
Affiliation  

Helicobacter pylori was reported as an important cause of gastritis, and gastric ulcers and CagA oncoprotein-producing H. pylori subgroups were blamed to increase the severity of gastritis. Disparities were reported in that the presence of serum anti-CagA IgA was not parallel with CagA-positive H. pylori cohabitation. We hypothesized that the HLA-DQA1 ~ DQB1 haplotypes in human populations include protective haplotypes that more effectively present immunogenic CagA peptides and susceptible haplotypes with an impaired capacity to present CagA peptides. We recruited patients (n = 201) admitted for gastroendoscopy procedures and performed high-resolution HLA-DQA1 and DQB1 typing. Serum anti-CagA IgA levels were analyzed by ELISA (23.0% positive), and H. pylori was classified as positive or negative in gastric mucosal tissue slides (72.6% positive). The HLA DQA1*05:05 allele (29.1%) and HLA DQB1*03:01 allele (32.8%) were found at the highest frequency among gastritis patients of Turkish descent. In HLA DQA1*05:05 ~ DQB1*03:01 double homozygous (7.3%) and heterozygous (40.7%) haplotype carriers, the presence of anti-CagA IgA decreased dramatically, the presence of H. pylori increased, and the presence of metaplasia followed a decreasing trend. The DQ protein encoded by HLA DQA1*05:05-DQ*03:01 showed a low binding affinity to the CagA peptide when binding capacity was analyzed by the NetMHCIIPan 4.0 prediction method. In conclusion, HLA DQA1 ~ DQB1 polymorphisms are crucial as host defense mechanisms against CagA H. pylori since antigen binding capacity plays a crucial role in anti-CagA IgA production.



中文翻译:

在土耳其胃炎队列中研究 HLA DQA1 ~ DQB1 单倍型、幽门螺杆菌感染、化生和抗 CagA IgA 血清阳性之间的关联

据报道,幽门螺杆菌是胃炎的重要病因,胃溃疡和产生 CagA 癌蛋白的幽门螺杆菌亚群被认为会增加胃炎的严重程度。据报道,血清抗 CagA IgA 的存在与 CagA 阳性幽门螺杆菌共存并不平行。我们假设人类中的 HLA-DQA1 ~ DQB1 单倍型包括更有效地呈递免疫原性 CagA 肽的保护性单倍型和呈递 CagA 肽的能力受损的易感性单倍型。我们招募了接受胃内窥镜检查的患者 ( n  = 201),并进行了高分辨率 HLA-DQA1 和 DQB1 分型。通过ELISA分析血清抗CagA IgA水平(23.0%阳性),并在胃粘膜组织切片中将幽门螺杆菌分为阳性或阴性(72.6%阳性)。HLA DQA1*05:05 等位基因 (29.1%) 和 HLA DQB1*03:01 等位基因 (32.8%) 在土耳其裔胃炎患者中出现频率最高。在 HLA DQA1*05:05 ~ DQB1*03:01 双纯合(7.3%)和杂合(40.7%)单倍型携带者中,抗 CagA IgA 的存在显着减少,幽门螺杆菌的存在增加并且化生呈减少趋势。当通过NetMHCIPan 4.0预测方法分析结合能力时,HLA DQA1*05:05-DQ*03:01编码的DQ蛋白显示出与CagA肽的低结合亲和力。总之,HLA DQA1 ~ DQB1 多态性作为针对 CagA幽门螺杆菌的宿主防御机制至关重要,因为抗原结合能力在抗 CagA IgA 产生中起着至关重要的作用。

更新日期:2023-11-18
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