Ji Lili, Zhan Yanxia, Wu Boting, Chen Pu, Cheng Luya, Ke Yang, Zhuang Xibing, Hua Fanli, Sun Lihua, Chen Hao, Li Feng, Cheng Yunfeng
Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai 200031, China.
Department of Transfusion Medicine, Zhongshan Hospital, Fudan University, Shanghai 200031, China.
J Clin Med. 2022 Sep 26;11(19):5665. doi: 10.3390/jcm11195665.
Primary immune thrombocytopenia (ITP) is an autoimmune disorder. The existence of autoreactive T cells has long been proposed in ITP. Yet the identification of autoreactive T cells has not been achieved, which is an important step to elucidate the pathogenesis of ITP. ITP patients' peripheral blood was collected prior to the treatment and one month after initiating dexamethasone treatment per related therapeutic guideline. Serum cytokines were profiled to examine T cell subtypes imbalance using a protein chip. TCR Vβ analysis in CD8T cells of ITP patients, and TCR CDR3 DNA sequencing of CD4T and CD8T cells were performed to determine the autoreactive T cells' clones. Cytokine profiling revealed imbalanced distribution of T cells subtypes, which was confirmed by CD4T and CD8T cells' oligoclonal expansion of TCR Vβ analysis and TCR CDR3 DNA sequencing. VDJ segments were found to be more frequently presented in ITP patients, when compared with health controls. There was an individualized CD4T cell or CD8+T cell CDR3 sequence in each ITP patient. The present study revealed that T cell clones expanded in ITP patients' peripheral blood, and each clone had an individualized TCR CDR3 sequence. The expanded T cell clones preferred to use some specific VDJ segment. Further studies are warranted to get access to individualized treatment such as Car-T in patients with ITP.
原发性免疫性血小板减少症（ITP）是一种自身免疫性疾病。长期以来，人们一直认为ITP中存在自身反应性T细胞。然而，尚未实现对自身反应性T细胞的鉴定，而这是阐明ITP发病机制的重要一步。按照相关治疗指南，在治疗前及开始地塞米松治疗1个月后采集ITP患者的外周血。使用蛋白质芯片分析血清细胞因子，以检测T细胞亚群失衡情况。对ITP患者的CD8T细胞进行TCR Vβ分析，并对CD4T和CD8T细胞进行TCR CDR3 DNA测序，以确定自身反应性T细胞的克隆。细胞因子分析显示T细胞亚群分布失衡，这通过TCR Vβ分析和TCR CDR3 DNA测序的CD4T和CD8T细胞寡克隆扩增得到证实。与健康对照相比，发现VDJ片段在ITP患者中更频繁出现。每个ITP患者都有一个个体化的CD4T细胞或CD8+T细胞CDR3序列。本研究表明，ITP患者外周血中T细胞克隆扩增，且每个克隆都有一个个体化的TCR CDR3序列。扩增的T细胞克隆倾向于使用某些特定的VDJ片段。有必要进行进一步研究，以便为ITP患者提供如嵌合抗原受体T细胞（Car-T）等个体化治疗。
