Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Maebashi, Japan.
Department of Anatomy and Cell Biology, Hyogo College of Medicine, Maebashi, Japan.
Br J Haematol. 2018 Mar;180(5):705-714. doi: 10.1111/bjh.15085. Epub 2018 Jan 23.
Programmed death-1 (PD-1, PDCD1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4, CTLA4) play central roles in immune checkpoint pathways. Single nucleotide polymorphisms (SNPs) of PDCD1 and CTLA4 have been reported to be associated with susceptibility to some autoimmune diseases. However, the potential association between SNPs in these immune checkpoint genes and risk of chronic immune thrombocytopenia (cITP) remain controversial and obscure. The aims of this study were to clarify the influence of PDCD1 and CTLA4 SNPs on the risk of developing cITP and its clinical features. We obtained genomic DNA from 119 patients with cITP and 223 healthy controls; their genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Patients with cITP had a significantly higher frequency of the PDCD1 +7209 TT genotype compared with healthy controls. The CTLA4 -1577 GG genotype and CT60 GG genotype showed higher frequencies of platelet count <5 × 10 /l at diagnosis, minimum platelet count <5 × 10 /l, and bleeding symptoms. Moreover, the PDCD1 -606 AA genotype and +63379 TT genotype were significantly associated with a lower number of patients who achieved a complete response to prednisolone treatment. Our results suggest that the immune checkpoint polymorphisms may affect the susceptibility to the clinical features of cITP, and treatment response of the affected patients.
程序性死亡受体-1（PD-1，PDCD1）和细胞毒性 T 淋巴细胞相关抗原-4（CTLA-4，CTLA4）在免疫检查点途径中发挥核心作用。已报道 PDCD1 和 CTLA4 的单核苷酸多态性（SNPs）与一些自身免疫性疾病的易感性有关。然而，这些免疫检查点基因中的 SNPs 与慢性免疫性血小板减少症（cITP）风险之间的潜在关联仍然存在争议和不清楚。本研究的目的是阐明 PDCD1 和 CTLA4 SNPs 对发展为 cITP 及其临床特征的风险的影响。我们从 119 例 cITP 患者和 223 例健康对照者中获得了基因组 DNA；通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法确定其基因型。与健康对照组相比，cITP 患者的 PDCD1 +7209 TT 基因型频率明显更高。CTLA4 -1577 GG 基因型和 CT60 GG 基因型在诊断时血小板计数<5×10 /l、最低血小板计数<5×10 /l 和出血症状的频率更高。此外，PDCD1 -606 AA 基因型和 +63379 TT 基因型与接受泼尼松龙治疗后达到完全缓解的患者数量减少显著相关。我们的研究结果表明，免疫检查点多态性可能影响 cITP 的易感性和受影响患者的治疗反应。
