Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXCR4 expression on memory CD4(+) T cells, and disease activity.
Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXCR4 expression on memory CD4(+) T cells, and disease activity.
复制标题
DOI：
10.1038/srep29338
复制
发表时间：
2016-07-07
影响因子：
4.6
通讯作者：
Yamamoto K
中科院分区：
文献类型：
--
作者：
Nagafuchi Y;Shoda H;Sumitomo S;Nakachi S;Kato R;Tsuchida Y;Tsuchiya H;Sakurai K;Hanata N;Tateishi S;Kanda H;Ishigaki K;Okada Y;Suzuki A;Kochi Y;Fujio K;Yamamoto K
类风湿性关节炎（RA）是一种慢性自身免疫性炎症性疾病，可导致破坏性关节炎。尽管HLA II类基因座是类风湿关节炎最强的遗传危险因素，但HLA II类等位基因与淋巴细胞活化之间的关系仍不清楚。我们对91例HLA-DRB 1基因型RA患者和110例健康献血员进行了外周血单个核细胞免疫表型分析。通过多元线性回归分析，记忆性CXCR 4 + CD 4 + T细胞的频率与疾病严重程度显著相关，而非Th 1和Th 17细胞。具有一个或多个易感HLA-DR单倍型（共享表位：SE）的RA患者显示记忆性CXCR 4 + CD 4 + T细胞的频率显著较高。此外，记忆性CXCR 4 + CD 4 + T细胞的频率与B细胞表面HLA-DR的表达水平显著相关，在RA伴SE患者中，其表达水平升高。体外分析和转录组学通路分析表明，HLA-DR与T细胞受体之间的相互作用是记忆性CXCR 4 + CD 4 + T细胞的重要调节因子。在临床上，记忆性CXCR 4 + CD 4 + T细胞的频率越高，预示着对CTLA 4-IG的反应越好。记忆性CXCR 4 + CD 4 + T细胞可能作为一种强有力的生物标志物，用于阐明HLA-DRB 1基因型与RA疾病活动性之间的联系。
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that leads to destructive arthritis. Although the HLA class II locus is the strongest genetic risk factor for rheumatoid arthritis, the relationship between HLA class II alleles and lymphocyte activation remains unclear. We performed immunophenotyping of peripheral blood mononuclear cells on 91 HLA-DRB1-genotyped RA patients and 110 healthy donors. The frequency of memory CXCR4+CD4+ T cells, and not Th1 and Th17 cells, was significantly associated with disease severity by multiple linear regression analysis. RA patients with one or more susceptible HLA-DR haplotypes (shared epitope: SE) displayed a significantly higher frequency of memory CXCR4+CD4+ T cells. Moreover, the frequency of memory CXCR4+CD4+ T cells significantly correlated with the expression level of HLA-DR on B cells, which was elevated in RA patients with SE. In vitro analysis and transcriptomic pathway analysis suggested that the interaction between HLA-DR and T cell receptors is an important regulator of memory CXCR4+CD4+ T cells. Clinically, a higher frequency of memory CXCR4+CD4+ T cells predicted a better response to CTLA4-Ig. Memory CXCR4+CD4+ T cells may serve as a powerful biomarker for unraveling the linkage between HLA-DRB1 genotype and disease activity in RA.