AUTHOR=Lin Dan , Zhu Rong-Cheng , Tang Chun , Li Fen-Fen , Gao Mei-Ling , Wang Yu-Qin 

TITLE=Association of TIM-3 with anterior uveitis and associated systemic immune diseases: a Mendelian randomization analysis

JOURNAL=Frontiers in Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1183326

DOI=10.3389/fmed.2023.1183326

ISSN=2296-858X

ABSTRACT=<sec><title>Background</title><p>We aimed to investigate the causal association between <italic>TIM-3</italic>, an immune checkpoint inhibitor, and anterior uveitis (AU), as well as associated systemic immune diseases.</p></sec><sec><title>Materials and methods</title><p>We performed two-sample Mendelian randomization (MR) analyses to estimate the causal effects of <italic>TIM-3</italic> on AU and three associated systemic diseases, namely ankylosing spondylitis (AS), Crohn's disease (CD), and ulcerative colitis (UC). Single-nucleotide polymorphisms (SNPs) associated with AU, AS, CD, and UC were selected as the outcomes: AU GWAS with 2,752 patients with acute AU accompanied with AS (cases) and 3,836 AS patients (controls), AS GWAS with 968 cases and 336,191 controls, CD GWAS with 1,032 cases and 336,127 controls, and UC GWAS with 2,439 cases and 460,494 controls. The <italic>TIM-3</italic> dataset was used as the exposure (<italic>n</italic> = 31,684). Four MR methods, namely, inverse-variance weighting (IVW), MR-Egger regression, weighted median, and weighted mode, were used in this study. Comprehensive sensitivity analyses were conducted to estimate the robustness of identified associations and the potential impact of horizontal pleiotropy.</p></sec><sec><title>Results</title><p>Our studies show that <italic>TIM-3</italic> is significantly associated with CD using the IVW method (OR = 1.001, 95% CI = 1.0002–1.0018, <italic>P</italic>-value = 0.011). We also found that <italic>TIM-3</italic> may be a protective factor for AU although these results lacked significance (OR = 0.889, 95% CI = 0.631–1.252, <italic>P</italic>-value = 0.5). No association was observed between the genetic predisposition to particular <italic>TIM-3</italic> and susceptibility to AS or UC in this study. No potential heterogeneities or directional pleiotropies were observed in our analyses.</p></sec><sec><title>Conclusion</title><p>According to our study, a small correlation was observed between <italic>TIM-3</italic> expression and CD susceptibility. Additional studies in different ethnic backgrounds will be necessary to further explore the potential roles and mechanisms of TIM-3 in CD.</p></sec>