Variation in genes implicated in B-cell maturation and antibody production affects susceptibility to pemphigus.,Immunology

当前位置： X-MOL 学术 › Immunology › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Variation in genes implicated in B-cell maturation and antibody production affects susceptibility to pemphigus.
Immunology ( IF 4.9 ) Pub Date : 2020-09-14 , DOI: 10.1111/imm.13259
Verónica Calonga-Solís ₁ , Leonardo M Amorim ₁ , Ticiana D J Farias ₁ , Maria Luiza Petzl-Erler ₁ , Danielle Malheiros ₁ , Danillo G Augusto _{1,

2}

Affiliation

Pemphigus foliaceus (PF) is an autoimmune blistering skin disease characterized by the presence of pathogenic autoantibodies against desmoglein 1, a component of intercellular desmosome junctions. PF occurs sporadically across the globe and is endemic in some Brazilian regions. Because PF is a B‐cell‐mediated disease, we aimed to study the impact of variants within genes encoding molecules involved in the different steps of B‐cell development and antibody production on the susceptibility of endemic PF. We analysed 3,336 single nucleotide polymorphisms (SNPs) from 167 candidate genes genotyped with Illumina microarray in a cohort of 227 PF patients and 193 controls. After quality control and exclusion of non‐informative and redundant SNPs, 607 variants in 149 genes remained in the logistic regression analysis, in which sex and ancestry were included as covariates. Our results revealed 10 SNPs within or nearby 11 genes that were associated with susceptibility to endemic PF (OR >1.56; p < 0.005): rs6657275*G (TGFB2); rs1818545*A (RAG1/RAG2/IFTAP);rs10781530*A (PAXX), rs10870140*G and rs10781522*A (TRAF2); rs535068*A (TNFRSF1B); rs324011*A (STAT6);rs6432018*C (YWHAQ); rs17149161*C (YWHAG); and rs2070729*C (IRF1). Interestingly, these SNPs have been previously associated with differential gene expression, mostly in peripheral blood, in publicly available databases. For the first time, we show that polymorphisms in genes involved in B‐cell development and antibody production confer differential susceptibility to endemic PF, and therefore are candidates for possible functional studies to understand immunoglobulin gene rearrangement and its impact on diseases.

中文翻译：

与 B 细胞成熟和抗体产生有关的基因变异会影响天疱疮的易感性。

落叶型天疱疮 (PF) 是一种自身免疫性水疱性皮肤病，其特征是存在针对桥粒芯糖蛋白 1（细胞间桥粒连接的组成部分）的致病性自身抗体。 PF 在全球范围内零星发生，在巴西一些地区呈地方性流行。由于 PF 是一种 B 细胞介导的疾病，我们旨在研究参与 B 细胞发育和抗体产生不同步骤的基因编码分子变异对地方性 PF 易感性的影响。我们分析了 227 名 PF 患者和 193 名对照人群中使用 Illumina 微阵列进行基因分型的 167 个候选基因的 3,336 个单核苷酸多态性 (SNP)。经过质量控制并排除无信息和冗余的 SNP 后，149 个基因的 607 个变异仍保留在逻辑回归分析中，其中性别和血统被纳入作为协变量。我们的结果显示 11 个基因内或附近的 10 个 SNP 与地方性 PF 易感性相关（OR >1.56； p < 0.005）： rs6657275*G ( TGFB2 )； rs1818545*A （ RAG1 / RAG2 / IFTAP） ； rs10781530*A （ PAXX ）、 rs10870140*G和rs10781522*A （ TRAF2 ）； rs535068*A ( TNFRSF1B ); rs324011*A （ STAT6） ； rs6432018*C ( YWHAQ) ; rs17149161*C ( YWHAG) ;和rs2070729*C ( IRF1) 。有趣的是，这些 SNP 先前已在公开数据库中与差异基因表达相关，主要是在外周血中。我们首次表明，参与 B 细胞发育和抗体产生的基因多态性赋予对地方性 PF 的不同易感性，因此是可能的功能研究的候选者，以了解免疫球蛋白基因重排及其对疾病的影响。

更新日期：2020-09-14

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11