The amino acid variation within the binding pocket 7 and 9 of HLA-DRB1 molecules are associated with primary Sjogren's syndrome

被引：19

作者：

Huang, Renliang ^{[1
]}

Yin, Junping ^{[1
]}

Chen, Yan ^{[1
]}

Deng, Fengyuan ^{[1
]}

Chen, Juan ^{[4
]}

Gao, Xing ^{[5
]}

Liu, Zuguo ^{[1
]}

Yu, Xinhua ^{[1
,2
,3
]}

Zheng, Junfeng ^{[1
,4
]}

机构：

[1] Xiamen Univ, Coll Med, Xiamen 361005, Peoples R China

[2] Res Ctr Borstel, Prior Area Asthma & Allergy, D-23845 Borstel, Germany

[3] UGMLC, Airway Res Ctr North ARCN, Bad Nauheim, Germany

[4] Xiamen Univ, Affiliated Hosp 1, Xiamen 361005, Peoples R China

[5] Xiamen Univ Hosp, Xiamen, Peoples R China

来源：

JOURNAL OF AUTOIMMUNITY | 2015年 / 57卷

基金：

中国国家自然科学基金;

关键词：

Sjogren's syndrome; Autoimmunity; HLA; Peptide binding groove; Homology modeling; HLA CLASS-II; CRYSTAL-STRUCTURE; SUSCEPTIBILITY; PEPTIDE; GENES; DRA-ASTERISK-0101; POLYMORPHISM; CHINESE;

D O I：

10.1016/j.jaut.2014.11.006

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Primary Sjogren's syndrome (pSS) is associated with HLA-DRB1 loci, but the association of amino acid variations in the hypervariable region of the HLA-DR beta 1 chain with pSS is largely unknown. In this study, we aimed to identify the amino acid variations within the hypervariable region of HLA-DRB1 molecule which are associated with the susceptibility to pSS. We sequenced the 2nd exon of the HLA-DRB1 locus in 52 pSS patients and 179 controls. The HLA-DRB1*0803 is the allele that shows the strongest association with pSS in Chinese population (OR = 3.0, P = 2.4 x 10(-4)). Furthermore, amino acid variations within the binding pocket P7 and P9 are associated with the susceptibility to pSS. An interaction between two residues within P7, beta 47 and beta 67, is associated with pSS. Structural modeling studies demonstrated that the electrostatics of peptide binding pocket 9 are opposite in pSS-susceptible and -protective HLA-DRB1 alleles. In conclusion, our results suggest that structural heterogeneity of the HLA-DRB1 peptide binding pocket P7 and P9 might play a role in the pathogenesis of pSS. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：53 / 59

页数：7

共 22 条

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