Causal association between immune cytokines and psoriasis: A two-way Mendelian randomization study

The aim of this research was to explore the potential causal links between various immune cell profiles and the risk of psoriasis, employing a systematic two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) model is the most commonly used two-sample MR analysis method for estimating the causal effect of exposure on outcomes. In addition to the IVW, we also used the weighted median method, the MR Egger method, and Steiger test as sensitivity analyses. Sensitivity analyses were performed using Cochran Q test for both IVW and MR Egger methods. The MR Egger intercept test was performed to assess horizontal multidimensionality by testing instrumental variables. All 4 immune cells associated with HLA DR (HLA DR++ monocyte %leukocyte, HLA DR on CD14+ CD16- monocyte, HLA DR on CD14+ monocyte, and HLA DR on monocyte) exhibited a significant negative correlation with psoriasis. Further analysis demonstrated that the performance of HLA DR on CD14+ CD16- monocyte and HLA DR on CD14+ monocyte was consistent and robust across multiple tests, with no significant heterogeneity or horizontal pleiotropy observed. This study corroborates the protective role of these 4 immune cells in psoriasis, with a particular focus on HLA DR on CD14+ CD16- monocytes and HLA DR on CD14+ monocytes.