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通过高通量测序对强直性脊柱炎患者外周血TCR库进行表征。

Characterization of peripheral blood TCR repertoire in patients with ankylosing spondylitis by high-throughput sequencing.

作者信息

Cui Jin-Huan, Jin Ya-Bin, Lin Kai-Rong, Xiao Ping, Chen Xiang-Ping, Pan Ying-Ming, Lin Wei, Wu Zu-Chang, Guo Dong-Mei, Mao Xiao-Fan, Zhang Chu-Ling, Lian Wen-Lue, Luo Wei

机构信息

Clinical Research Institute, Foshan Hospital, Sun Yat-sen University, Foshan 528000, Guangdong, China.

Department of Rheumatology, Foshan Hospital, Sun Yat-sen University, Foshan 528000, Guangdong, China.

出版信息

Hum Immunol. 2018 Jun;79(6):485-490. doi: 10.1016/j.humimm.2018.03.007. Epub 2018 Mar 31.

Abstract

Ankylosing spondylitis (AS) is a chronic and progressive autoimmune disease affecting the invasion of the spine, sacroiliac joints and peripheral joints. T cells play a vital role in the underlying pathogenesis of AS, which mediated autoimmune and inflammatory responses via specific recognition of autoantigen peptides presented by susceptibility HLA. Antigen-specific T cells triggered by HLA/antigen complexes will undergo a massive expansion that forming an uneven T cell repertoire. To enhance our understanding of T-cell-mediated autoimmune in AS, we applied TCR β chains high-throughput sequencing to AS patients for in-depth TCR repertoire analysis. A significantly lower TCR repertoire diversity was observed in peripheral blood of AS patients relative to controls. And severe patients in our AS cohort have a more restricted TCR repertoire than mild patients, suggesting that the TCR repertoire diversity might be associated with the clinical severity of disease. No V, J and VJ pairs with significant biased usage were identified, which indicated that the usage frequency deviation of certain V/J/V-J genes in AS patients is little. This is a pilot study with potentially interesting observation on reduced diversity of T cells repertoire in peripheral blood of AS patients and further studies are needed.

摘要

强直性脊柱炎(AS)是一种慢性进行性自身免疫性疾病,会影响脊柱、骶髂关节和外周关节。T细胞在AS的潜在发病机制中起着至关重要的作用,它通过特异性识别易感HLA呈递的自身抗原肽来介导自身免疫和炎症反应。由HLA/抗原复合物触发的抗原特异性T细胞会发生大量扩增,从而形成不均衡的T细胞库。为了加深我们对AS中T细胞介导的自身免疫的理解,我们对AS患者应用TCRβ链高通量测序进行深入的T细胞库分析。相对于对照组,AS患者外周血中观察到T细胞库多样性显著降低。并且我们AS队列中的重症患者比轻症患者的T细胞库更受限,这表明T细胞库多样性可能与疾病的临床严重程度相关。未发现有明显偏向性使用的V、J和VJ对,这表明AS患者中某些V/J/V-J基因的使用频率偏差很小。这是一项初步研究,对AS患者外周血中T细胞库多样性降低有潜在有趣的观察结果,还需要进一步研究。

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