Causal role of immune cells in chronic obstructive pulmonary disease: Mendelian randomization study

Innate and adaptive immunity play different roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, previous studies on the relationship between immune cells and COPD reported inconsistent results.

The causal connection between 731 immune cells and COPD was established using a two-sample Mendelian randomization (MR) analysis through publicly accessible genetic data. The heterogeneity and horizontal pleiotropism of the findings were confirmed using sensitivity analysis.

In the B-cell panel, B-cell activating factor receptor (BAFF-R) on CD20^- and CD20 on IgD^-CD38^bright (OR (95% CI): 0.93 (0.88, 0.99) and 0.97 (0.95, 0.98), respectively) were discovered to be protective. In the cDC panel, CD62L^- plasmacytoid DC AC, CD80 on monocytes and CD11c on myeloid DCs (OR (95% CI): 0.94 (0.92, 0.97), 0.97 (0.94, 0.99) and (0.97 (0.95, 0.98), respectively) exerted protective effects. However, unswitched memory AC (OR (95%CI): 1.08 (1.01,1.15)) and CD 19 on IgD^- CD 27^- (OR (95%CI): 1.06 (1.02,1.10)) were hazardous in the B-cell panel. However, among the 731 immune cell phenotypes, no causal relationship was found for COPD on immune cells.

This study found a potential causal relationship between immune cells in COPD, ruling out reverse causation. This study provides new avenues for studying the mechanisms of COPD.