Yu Jiang, Shi Bin, Ma Long, Liu Chunmei, Sun Suhong, Ma Rui, Qiu Yuehong, Yao Xinsheng
Department of Immunology, Research Center for Medicine & Biology, Innovation & Practice Base for Graduate Students Education, Zunyi Medical University Cell Engineering Laboratory, The first Affiliated Hospital of ZunYi Medical University Department of Laboratory Medicine, Zunyi Medical University Department of Nephropathy and Rheumatology Department of Breast Surgery, The first Affiliated Hospital of ZunYi Medical University, Zunyi Department of Gastroenterology, Rizhao People's Hospital, Rizhao, China.
Medicine (Baltimore). 2017 Dec;96(49):e9022. doi: 10.1097/MD.0000000000009022.
High-dose glucocorticoid therapy has been widely applied in clinical practice in systemic lupus erythematosus (SLE)patients, but less is known about the changes of T cells, especially the T cell receptor (TCR) repertoires, during the treatment. The aim of this paper is to describe the changes of TCR that recurrent and new-onset SLE patients treated by high-dose glucocorticoid therapy.
Drugs of clinical treatment of SLE mainly include glucocorticoid, immunosuppressive agents, nonsteroidal anti-inflammatory drugs and B cell targeted drugs, etc, but the clinical symptoms were in remission and recurrent of onset patients with SLE.
Refer to the diagnostic criteria for SLE in 2011 by the American society of rheumatology.
All patients were treated with High-dose glucocorticoid therapy and surveyed the TCR repertoires at 3 monitoring moments (before treatment, one month after treatment, and 3 months after treatment) to analyze the relationship between the characteristics of TCR repertoire and the highdose glucocorticoid therapy.
We found that high-dose glucocorticoid therapy resulted in clinical symptom remission, as well as change of diversity, highly expanded clones (HEC), usage of TCR beta chain variable gene (TRBV)/TCR beta chain joining gene (TRBJ), and overlapped sequences of TCR beta chain complementarity determining region 3 (CDR3) repertoires. This suggests that the effect of high-dose glucocorticoids on TCR repertoires is closely related to individual autoimmune T cells.
In this study, we have shown that we could evaluate the effect of therapy, the pathogenesis, and the prognosis for the patients with SLE by monitoring the TCR CDR3 repertoires. It could afford a new method to find the therapeutic target of SLE.
大剂量糖皮质激素疗法已在系统性红斑狼疮(SLE)患者的临床实践中广泛应用,但对于治疗期间T细胞的变化,尤其是T细胞受体(TCR)库的变化,人们了解较少。本文旨在描述接受大剂量糖皮质激素疗法的复发和新发SLE患者的TCR变化。
SLE的临床治疗药物主要包括糖皮质激素、免疫抑制剂、非甾体抗炎药和B细胞靶向药物等,但SLE患者的临床症状仍有缓解和复发。
参照美国风湿病学会2011年SLE的诊断标准。
所有患者均接受大剂量糖皮质激素治疗,并在3个监测时间点(治疗前、治疗后1个月和治疗后3个月)检测TCR库,以分析TCR库特征与大剂量糖皮质激素治疗之间的关系。
我们发现大剂量糖皮质激素治疗导致临床症状缓解,以及TCR库的多样性、高度扩增克隆(HEC)、TCRβ链可变基因(TRBV)/TCRβ链连接基因(TRBJ)的使用和TCRβ链互补决定区3(CDR3)库重叠序列的变化。这表明大剂量糖皮质激素对TCR库的影响与个体自身免疫性T细胞密切相关。
在本研究中,我们表明通过监测TCR CDR3库可以评估SLE患者的治疗效果、发病机制和预后。这可以为寻找SLE的治疗靶点提供一种新方法。