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

doi:10.3389/fimmu.2021.607966

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

Front Immunol. 2021 Feb 24:12:607966. doi: 10.3389/fimmu.2021.607966. eCollection 2021.

Authors

Xiaosheng Huang^{1

2}, Xinhua Liu^{1

2}, Ye Ye², Tong Zhang¹, Shaoyi Mei^{1

2}, Tianhui Zhu^{1

2}, Shiming Peng^{1

2}, Jiamin Cai², Zonghui Yan^{1

2}, Kun Zeng^{1

2}, Danyao Nie^{1

2}, Liangnan Sun^{1

2}, Xiaofeng Hou¹, Jun Zhao³

Affiliations

¹ Shenzhen Eye Institute, Shenzhen Eye Hospital, Jinan University, Shenzhen, China.
² School of Ophthalmology, Optometry, Shenzhen Eye Hospital, Shenzhen University, Shenzhen, China.
³ Department of Ophthalmology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.

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 (P_c ) = 0.037; P_c = 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 (P_c = 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.

Keywords: CTLA-4; PD-1; Posner-Schlossman syndrome; genetic variants; soluble molecular.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Alleles
Biomarkers
CTLA-4 Antigen / genetics*
Case-Control Studies
China
Female
Gene Frequency
Genetic Association Studies* / methods
Genetic Predisposition to Disease*
Genotype
Haplotypes
Humans
Immune Checkpoint Proteins / blood*
Immune Checkpoint Proteins / genetics*
Linkage Disequilibrium
Male
Middle Aged
Polymorphism, Single Nucleotide*
Programmed Cell Death 1 Receptor / genetics*

Substances

Biomarkers
CTLA-4 Antigen
CTLA4 protein, human
Immune Checkpoint Proteins
Programmed Cell Death 1 Receptor