Causal relationships between immune cells, inflammatory cytokines, and pertussis: Bidirectional 2-sample Mendelian randomization study and mediation analysis

Studies have shown that immune cells play an important role in the occurrence and development of pertussis, but the specific causal relationships are yet to be determined. Additionally, inflammatory cytokines, as regulators of immune responses, may mediate the relationship between immune cells and pertussis, and the specific mechanisms involved require further exploration. This study utilizes data from multiple large-scale genome-wide association studies, covering 731 types of immune cells and 91 types of inflammatory cytokines. The bidirectional 2-sample Mendelian randomization (MR) method is employed, with inverse-variance weighted as the main statistical approach, to assess the causal relationships between immune cells, inflammatory cytokines, and pertussis. Furthermore, a 2-step MR method is used to investigate the mediating role of inflammatory cytokines in the effect of immune cells on pertussis. Our study results indicate that 11 types of immune cells have a protective effect against pertussis, with the strongest protection observed from CD25 on CD28+ CD4+ cells (OR = 0.3533, CI = 0.1636–0.7627, P = .008). Conversely, 19 types of immune cells are positively associated with the risk of pertussis, with the strongest correlation found in CD3− lymphocyte %lymphocyte (OR = 3.6613, CI = 1.5012–8.299, P = .0043). Additionally, 3 inflammatory cytokines – IL-4, IL-18R1, and FGF-21 – show a causal relationship with pertussis. Our mediation MR results indicate that inflammatory cytokines do not act as mediators in the relationship between immune cells and pertussis. This study suggests a causal relationship between immune cells and pertussis, while inflammatory cytokines do not appear to be mediating factors in the pathway from immune cells to pertussis.