AUTHOR=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 

TITLE=Polymorphisms and Circulating Plasma Protein Levels of Immune Checkpoints (CTLA-4 and PD-1) Are Associated With Posner-Schlossman Syndrome in Southern Chinese

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.607966

DOI=10.3389/fimmu.2021.607966

ISSN=1664-3224

ABSTRACT=<p>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 <italic>CTLA-4</italic> (rs733618, rs4553808, rs5742909, rs231775, and rs3087243) and five SNPs of <italic>PD-1</italic> (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 <italic>CTLA-4</italic> were significantly higher in PSS patients than in healthy controls (corrected <italic>p</italic> (<italic>P<sub>c</sub></italic>) = 0.037; <italic>P<sub>c</sub></italic> = 0.044, respectively). The haplotype frequencies of CACGG haplotype (rs733618-rs4553808-rs5742909-rs231775-rs3087243) of <italic>CTLA-4</italic> and TGAGC haplotype (rs10204525-rs2227981-rs2227982-rs41386349-rs36084323) of <italic>PD-1</italic> in the PSS group was significantly lower than those in the control group (<italic>P<sub>c</sub></italic> = 0.015, <italic>p</italic> = 0.034, respectively). Circulating plasma levels of sCTLA-4 and sPD-1 in PSS patients were significantly higher than those in controls (all <italic>p</italic> &lt; 0.001). The present study suggests that <italic>CTLA-4</italic> and <italic>PD-1</italic> 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.</p>