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

Xiaosheng Huang,Tong Zhang,Tianhui Zhu,Shiming Peng,Jiamin Cai,Xinhua Liu,Kun Zeng,Jun Zhao,Xiaofeng Hou,Shaoyi Mei,Ye Ye,Danyao Nie,Zonghui Yan,Liangnan Sun

doi:10.3389/fimmu.2021.607966

Abstract

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

Highlights

Posner-Schlossman syndrome (PSS) is eponymously named after Posner and Schlossman who first described this condition in 1948 [1]
Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and PD-1, the most widely investigated checkpoints, are reportedly upregulated by the tumor to escape from immune system monitoring [10]
The frequencies of T allele of rs733618 and A allele of rs231775 in CTLA-4 were significantly higher in PSS patients than in controls, and these associations survived multiple testings correction

Summary

Introduction

Posner-Schlossman syndrome (PSS) is eponymously named after Posner and Schlossman who first described this condition in 1948 [1]. Some previous studies have found that the adaptive immune system was dysfunctional in patients with PSS. Pohlmann et al found that the expression level of Th1 immune mediator significantly increased in the aqueous humor of patients with PSS [5]. Our previous research showed that the Th1- and Th17-related cytokines in the serum might not contribute to PSS [4]. Human leukocyte antigen (HLA) allelic heterogenicity might contribute to some differences in PSS prevalence among ethnic populations. Hirose et al reported that the HLA-Bw54 and HLABw54-Cw1 haplotype were overrepresented in patients with PSS in a Japanese population [6]. We found that the HLA-C*14:02 and HLA-E*01:03 alleles, and the HLAA*11:01-C*14:02, HLA-B*51:01-C*14:02, and HLA-E*01:03G*01:04 haplotypes confer susceptibility to PSS in a southern Chinese population [7, 8]. The role of non-HLA genetic variants in PSS still needs to be investigated

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