The Causal Nexus of Immune Cells and Vitiligo: A Genetic Perspective

ObjectiveThis study aims to explore the causal relationship between 731 immune cell traits and vitiligo using Mendelian randomization. MethodsWe used a two-sample Mendelian randomization (MR) analysis, employing genetic variations extracted from genome-wide association studies (GWAS) as instrumental variables (IVs). Data sources included immune phenotype data from 3,757 European individuals and data from FinnGen, comprising a total of 385,538 samples (292 cases and 385,509 controls). The study used the inverse-variance weighted (IVW) method as the primary analysis method and conducted various robustness tests through median-based weighted analysis, mode-based weighted analysis, and the MR-Egger method to control for false positive results in multiple hypothesis testing. ResultsOur study found that the pathogenesis of vitiligo may significantly reduce the levels of the following immune cells: TD CD4+ %T cells (b=-0.458, 95% CI=0.17-0.76, PFDR=0.015, P=0.000), CD25 on CD39+ CD4+ cells (b=-0.155, 95% CI=0.78-0.94, PFDR=0.166, P=0.769), and CD4 on HLA DR+ CD4+ cells (b=-0.431, 95% CI=0.50-0.85, PFDR=0.166, P=0.001). Additionally, the causal effect estimate of vitiligo on CCR2 on monocyte is 0.75 (b=-0.290, 95% CI=0.64-0.88, PFDR=0.114, P=0.828), and a negative association was also found on FSC-A on NK cells (b=-0.481, 95% CI=0.47-0.82, PFDR=0.142, P=0.197). On the other hand, our study suggests that the occurrence of vitiligo may increase the levels of CD28 on CD28+ CD45RA+ CD8br cells (b=0.311, 95% CI=1.13-1.65, PFDR=0.166, P=0.393). ConclusionThe results of this study reveal causal links between vitiligo and multiple immune cell traits, highlighting the important role of the immune system in the pathogenesis of vitiligo. These findings provide new research directions for controlling vitiligo through immune regulation and may pave the way for early intervention and treatment strategies.