关键词: DMARDs T-cell receptor repertoire biomarkers next-generation sequencing rheumatoid arthritis

Mesh : Humans Arthritis, Rheumatoid / drug therapy genetics Antirheumatic Agents / therapeutic use Cohort Studies Clone Cells Receptors, Antigen, T-Cell / genetics

来  源:   DOI:10.1111/jcmm.17623

Abstract:
T-cell receptor repertoire (TCRR) sequencing has been widely applied in many fields as a novel tool. This study explored characteristics of TCRR in detail with a cohort of 598 rheumatoid arthritis (RA) patients before and after anti-rheumatic treatments. We highlighted the abnormal TCRR distribution in RA characterized by decreased diversity and increased proportion of hyperexpanded clones (HECs), which was potentially attributed to skewed usage of global V/J segments but not a few certain ones. Enriched motifs analysis in RA community demonstrated the huge heterogeneity of CDR3 sequences, so that individual factors are strongly recommended to be taken into consideration when it comes to clinical application of TCRR. Disease-modifying antirheumatic drugs (DMARDs) can regulate immune system through recovery of TCRR richness to relieve symptoms. Remarkably, sensitive gene profile and advantageous gene profile were identified in this study as new biomarkers for different DMARDs regimens.
摘要:
T细胞受体库(TCRR)测序作为一种新的工具在许多领域得到了广泛的应用。本研究通过598例类风湿关节炎(RA)患者在抗风湿治疗前后的队列,详细探讨了TCRR的特征。我们强调了RA中异常的TCRR分布,其特征是多样性降低和超扩张克隆(HECs)比例增加,这可能归因于全球V/J段的使用偏差,但不是少数。RA群落中丰富的基序分析证明了CDR3序列的巨大异质性,因此,强烈建议在TCRR的临床应用中考虑个体因素。抗风湿抗病药(DMARDs)可以通过恢复TCRR丰富度来调节免疫系统以缓解症状。值得注意的是,在这项研究中,敏感基因谱和有利基因谱被鉴定为不同DMARDs方案的新生物标志物.
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