Causal Involvement of Immune Cells in Chronic Obstructive Pulmonary Disease: A Mendelian Randomization Study

Background: The immune cells play a substantial role in the development and progression of chronic obstructive pulmonary disease (COPD). We aim to investigate the causal involvement of immune cells in COPD via a Mendelian randomization (MR) analysis. Methods: Published genome-wide association studies (GWAS) statistics on immune cells were analyzed, with genetic variants identified as instrumental variables (IVs). Inverse-variance weighting (IVW), weighted median, and MR-Egger regression methods were employed, along with simple mode and weighted mode adopted in the two-sample MR analysis. Sensitivity analysis was conducted to examine the heterogeneity, horizontal pleiotropy, and stability of the causal relationship. Results: IVW results suggested that CCR2 on CD62L+ plasmacytoid dendritic cells (DC), CCR2 on plasmacytoid DC, CD11b on CD66b++ myeloid cells, CD19 on CD20- CD38- CD24+ memory B cell subset, CD25 on transitional B cells, and CD25++CD8br % CD8br T cells were risk factors for the development of COPD. Besides, CD127 on effector memory-like cytotoxic T lymphocytes lacking expression of co-stimulatory molecule 28 (CD28-EM CTLs) and HLA DR+ NK ACs expressing human leukocyte antigen DR molecules while being natural killer cells (%NK ACs) were protective factors for COPD. Conclusion: This study unveiled a causal relationship between immune cell phenotype and COPD. These findings offer new insights for the prevention and treatment of COPD using COPD-associated immune cells.