Xudong Wang,1,2,* Shaoyu Guan,3,* Zhikuan Xia,2 Xin Zhang,2 Yu Bai,2 Qiang Li,4 Haitao Li,2 Rongya Yang2 

1Southern Medical District of Chinese PLA General Hospital, Beijing, 100843, People’s Republic of China; 2Department of Dermatology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100010, People’s Republic of China; 3Pharmaceutical Sciences Research Division, Department of Pharmacy, Medical Supplies Centre of PLA General Hospital, Beijing, 100853, China; Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 4Medical Health Care Department, Air Force Medical Center PLA, Beijing, 100142, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Rongya Yang, Department of Dermatology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100010, People’s Republic of China, Email yangrya@sina.com Haitao Li, Department of Dermatology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100010, People’s Republic of China, Email 343266881@qq.com

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.

Keywords: circulating immune cells, acne, Mendelian randomization, genome wide association study