Comprehensive Immune Landscape in Allergic Conjunctivitis: Insights from Mendelian Randomization Analysis.

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.