Investigating the Impact of Circulating Immune Cells on Acne Using Mendelian Randomization.

Background: While growing evidence suggests the intricate relationship between immune cells and the pathogenesis of acne, the causative implications underlying these associations remain poorly characterized. This study aimed to elucidate the causal links between various immune cell phenotypes and the development of acne using Mendelian randomization (MR) analysis.

Methods: Leveraging data of 731 immune cell traits and acne from genome-wide association studies, we conducted a bidirectional MR analysis. Rigorous instrumental variables selection was followed by causal inference using five complementary methods, including MR-Egger, weighted median, simple mode, inverse variance weighted (IVW), and weighted mode methods. Heterogeneity and pleiotropy were evaluated using Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis.

Results: Genetically predicted alterations in 26 immune cell phenotypes demonstrated causal associations with acne risk. Notably, 18 immune cell types exhibited protective effects, such as CD25 on IgD+ (IVW: OR 0.922, 95% CI 0.868-0.979; p = 0.008), naive-mature B cell %lymphocytes (IVW: OR 0.824, 95% CI 0.698-0.972; p = 0.022), and CD19 on sw mem (IVW: OR 0.841, 95% CI 0.752-0.940; p = 0.002). Conversely, 8 immune cell types conferred increased risk, such as IgD+ CD38dim AC (IVW: OR 1.054, 95% CI 1.002-1.108; p = 0.043), CD25 on unsw mem (IVW: OR 1.058, 95% CI 1.005-1.114; p = 0.030), and CD28+ DN (CD4-CD8-) %DN (IVW: OR 1.117, 95% CI 1.019-1.225; p = 0.019). The absence of significant heterogeneity or horizontal pleiotropy (p > 0.05) strengthens the credibility to the observed associations.

Conclusion: In conclusion, this research provides compelling genetic evidence for causal immunomodulatory influences on acne development, thus laying the groundwork for future investigational efforts aimed at uncovering targeted therapeutic strategies in acne management.