The feature of TRGV and TRDV repertoire distribution and clonality in patients with immune thrombocytopenic purpura

Abstract

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.