Immunological determinants of pterygium pathogenesis: Mendelian randomization analysis of CD39 + CD8 + T cell proportions within the T cell compartment.

Pterygium is a common eye condition affecting populations in subtropical and tropical climates. Emerging research suggests immune cell imbalances play a critical role in ocular surface diseases, including pterygium. One immune cell subset of interest, CD39 + CD8 + T cells, has been linked to regulating inflammation in autoimmune and inflammatory disorders. This study investigates whether the proportion of CD39 + CD8 + T cells causally influences pterygium risk using Mendelian randomization (MR): a statistical approach that mimics randomized trials by leveraging genetic variants as proxies for exposure. We identified genetic markers (single nucleotide polymorphisms) strongly associated with CD39 + CD8 + T cell levels and applied 5 MR models (inverse variance weighted, MR-Egger, weight median, simple mode, and weighted mode) to estimate causal effects. The primary method, inverse variance weighted, combines genetic data across variants to assess overall impact. Results across all models consistently showed a significant causal link between higher CD39 + CD8 + T cell proportions and increased pterygium risk (odds ratio = 1.190), with no evidence of bias from confounding factors or reverse causation (all sensitivity analyses P > .05). Our study specifically targets the proportion of CD39 + CD8 + T cells within the overall T cell population, postulating that a heightened abundance of these cells is associated with an elevated risk of pterygium. However, limitations include reliance on genetic data without direct experimental validation in clinical samples and the complexity introduced by genetic diversity, which is a critical next step to confirm these findings.