Zhang Xueli, Chen Shaohua, Yang Lijian, Li Bo, Zhu Kanger, Li Yangqiu
Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
Hematology. 2009 Aug;14(4):237-44. doi: 10.1179/102453309X439755.
Chronic idiopathic (immune) thrombocytopenic purpura (ITP) is an autoimmune disorder in which anti-platelet antibodies induce platelet destruction due to an imbalanced immune response. Recently, data indicated the gammadelta(+)T cells may play an important role in autoimmune disease. Our previous study has shown the restricted expression of TRBV subfamilies and the alteration of peripheral TRBV repertoire pattern in the majority of ITP patients. In the present study, we further analyze the feature of TRGV and TRDV repertoire distribution and clonality in patients with ITP. The CDR3 size of three TRGV and eight TRDV subfamily genes were analyzed in peripheral blood mononuclear cells (PBMCs) from 11 cases with ITP, using RT-PCR and GeneScan techniques. To determine the expression level of TRGV subfamily genes, quantitative analysis of TRGV I-III subfamilies was performed by real-time PCR. TRGV I-III subfamilies could be detected in the most samples from ITP as well as in healthy controls. However, clonal expansion of TRGV was identified in five cases with ITP, which displayed polyclonality in all of samples from healthy controls. The expression level of all TRGV I-III subfamilies in ITP was significantly lower than that from healthy controls (p=0.048, 0.001, 0.035, respectively). The expression pattern of TRGV I-III repertoire in ITP was TRGV I>TRGV III>TRGV II, in contrast, TRGV II>TRGV I>TRGV II was found in healthy controls. TRDV 1 and TRDV 2 could be detected in most samples from ITP as well as in healthy controls, whereas TRDV 3 could be detected in only two out of 11 cases with ITP, which could be found in 90% of healthy controls (p=0.02). Oligoclonally expanded TRDV 1 and TRDV 2 T cells could be identified in the half of the ITP samples, with similar results in healthy control. In conclusion, the alteration of peripheral TRGV and TRDV repertoire pattern might play a role in the pathogenesis of immune-mediated platelet destruction in some cases with ITP.
慢性特发性（免疫性）血小板减少性紫癜（ITP）是一种自身免疫性疾病，其中抗血小板抗体由于免疫反应失衡而导致血小板破坏。最近，数据表明γδ(+)T细胞可能在自身免疫性疾病中起重要作用。我们之前的研究表明，大多数ITP患者中TRBV亚家族的表达受限以及外周TRBV库模式的改变。在本研究中，我们进一步分析了ITP患者中TRGV和TRDV库分布及克隆性的特征。使用RT-PCR和基因扫描技术，分析了11例ITP患者外周血单个核细胞（PBMC）中三个TRGV和八个TRDV亚家族基因的CDR3大小。为了确定TRGV亚家族基因的表达水平，通过实时PCR对TRGV I-III亚家族进行了定量分析。在大多数ITP样本以及健康对照中都能检测到TRGV I-III亚家族。然而，在5例ITP患者中发现了TRGV的克隆性扩增，而所有健康对照样本均显示为多克隆性。ITP中所有TRGV I-III亚家族的表达水平均显著低于健康对照（分别为p=0.048、0.001、0.035）。ITP中TRGV I-III库的表达模式为TRGV I>TRGV III>TRGV II，相比之下，健康对照中为TRGV II>TRGV I>TRGV II。在大多数ITP样本以及健康对照中都能检测到TRDV 1和TRDV 2，而在11例ITP患者中只有2例能检测到TRDV 3，90%的健康对照中可检测到（p=0.02）。在一半的ITP样本中可鉴定出寡克隆扩增的TRDV 1和TRDV 2 T细胞，健康对照中结果相似。总之，外周TRGV和TRDV库模式的改变可能在某些ITP病例的免疫介导血小板破坏发病机制中起作用。
