Abstract
Introduction: Current understanding of the immune landscape underlying allergic conjunctivitis (AC) remains rather limited. We investigated the potential association between circulating immunophenotypes and AC using Mendelian randomization (MR) methodology. Methods: Based on genome-wide association study (GWAS) summary-level statistics, a 2-sample MR was employed to analyze the bidirectional causal relationships between 731 circulating immunophenotypes and AC risk. Results: A total of 33 genetically predicted immunophenotypes were significantly associated with AC risk. A protective effect of 18 immunophenotypes against AC was found, such as CD3 on CD39+CD8br (inverse variance weighted [IVW] odds ratio [OR] = 0.936, 95% confidence interval [CI]: 0.925–0.985, p = 0.003) and CD25 on CD28+CD4+ (IVW OR = 0.921, 95% CI: 0.863–0.983, p = 0.013). Conversely, 15 immunophenotypes were found to be significantly associated with AC risk, such as CD25 on IgD–CD38dim (IVW OR = 1.042, 95% CI: 1.012–1.073, p = 0.006). Reverse MR based on these 33 genetically predicted immunophenotypes suggested that AC also had a significant influence on four circulating immune cells, including CD33–HLA DR–AC (IVW OR = 1.187, 95% CI: 1.034–1.362, p = 0.015), CD3 on CD39+CD8br (IVW OR = 0.876, 95% CI: 0.779–0.985, p = 0.027), HLA DR on CD14+monocyte (IVW OR = 0.831, 95% CI: 0.725–0.953, p = 0.008), and CD39 on CD39+secreting Treg (IVW OR = 1.123, 95% CI: 1.002–1.259, p = 0.046). Conclusion: Our study highlights the intricate association between immune cells and AC, providing a valuable basis for future mechanistic and therapeutic studies from an immunological perspective.
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