Huang Xiaosheng, Liu Xinhua, Ye Ye, Zhang Tong, Mei Shaoyi, Zhu Tianhui, Peng Shiming, Cai Jiamin, Yan Zonghui, Zeng Kun, Nie Danyao, Sun Liangnan, Hou Xiaofeng, Zhao Jun
Shenzhen Eye Institute, Shenzhen Eye Hospital, Jinan University, Shenzhen, China.
School of Ophthalmology, Optometry, Shenzhen Eye Hospital, Shenzhen University, Shenzhen, China.
Front Immunol. 2021 Feb 24;12:607966. doi: 10.3389/fimmu.2021.607966. eCollection 2021.
Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) are well-known key immune checkpoints that play a crucial dampening effect on regulating T-cell homeostasis and self-tolerance. In this study, we aimed to evaluate the association between immune checkpoints (CTLA-4 and PD-1) and Posner-Schlossman syndrome (PSS) in a southern Chinese population. A total of 137 patients with PSS and 139 healthy controls from a southern Chinese population were recruited. Five single nucleotide polymorphisms (SNPs) of (rs733618, rs4553808, rs5742909, rs231775, and rs3087243) and five SNPs of (rs10204525, rs2227981, rs2227982, rs41386349, and rs36084323) were genotyped by SNaPshot technique. Soluble CTLA-4 (sCTLA-4) and soluble PD-1 (sPD-1) were determined by ELISA and antibody array assay, respectively. The frequencies of T allele at rs733618 and A allele at rs231775 of were significantly higher in PSS patients than in healthy controls (corrected ( ) = 0.037; = 0.044, respectively). The haplotype frequencies of CACGG haplotype (rs733618-rs4553808-rs5742909-rs231775-rs3087243) of and TGAGC haplotype (rs10204525-rs2227981-rs2227982-rs41386349-rs36084323) of in the PSS group was significantly lower than those in the control group ( = 0.015, = 0.034, respectively). Circulating plasma levels of sCTLA-4 and sPD-1 in PSS patients were significantly higher than those in controls (all < 0.001). The present study suggests that and genetic polymorphisms are associated with the susceptibility to PSS in a southern Chinese population. The upregulated circulating plasma protein levels of sCTLA-4 and sPD-1 might provide some hints regarding the dysfunction of immune checkpoints in PSS during the active status.
细胞毒性T淋巴细胞相关蛋白4（CTLA-4）和程序性细胞死亡蛋白1（PD-1）是众所周知的关键免疫检查点，在调节T细胞稳态和自身耐受性方面发挥着至关重要的抑制作用。在本研究中，我们旨在评估中国南方人群中免疫检查点（CTLA-4和PD-1）与波斯纳-施洛斯曼综合征（PSS）之间的关联。共招募了137例来自中国南方人群的PSS患者和139名健康对照。采用SNaPshot技术对CTLA-4的5个单核苷酸多态性（SNP）（rs733618、rs4553808、rs5742909、rs231775和rs3087243）以及PD-1的5个SNP（rs10204525、rs2227981、rs2227982、rs41386349和rs36084323）进行基因分型。分别通过ELISA和抗体芯片检测法测定可溶性CTLA-4（sCTLA-4）和可溶性PD-1（sPD-1）。PSS患者中CTLA-4的rs733618位点T等位基因频率和rs231775位点A等位基因频率显著高于健康对照（校正P值（Pcorr）分别为0.037；0.044）。PSS组中CTLA-4的CACGG单倍型（rs733618-rs4553808-rs5742909-rs231775-rs3087243）频率和PD-1的TGAGC单倍型（rs10204525-rs2227981-rs2227982-rs41386349-rs36084323）频率显著低于对照组（P值分别为0.015，0.034）。PSS患者循环血浆中sCTLA-4和sPD-1水平显著高于对照组（所有P值均<0.001）。本研究表明，CTLA-4和PD-1基因多态性与中国南方人群PSS易感性相关。sCTLA-4和sPD-1循环血浆蛋白水平上调可能为PSS活动期免疫检查点功能障碍提供一些线索。
