Complex causal association between immune cells and psoriatic arthritis: A bidirectional Mendelian randomization...

Previous epidemiological research has shown that immune cells have a significant impact on the progression and development of psoriatic arthritis (PsA). However, the causal relationship between immune cell characteristics and PsA remains uncertain. A bidirectional 2-sample Mendelian randomization analysis was conducted, using data from publicly available genome-wide association studies. Four Mendelian randomization analysis methods were employed to assess the causal relationships between 731 immunological traits and PsA, with the inverse variance weighted method as the primary analysis. Multiple sensitivity analyses were carried out to confirm the reliability of the findings. After false discovery rate (FDR) adjustment, the genetically predicted inverse variance weighted methods revealed that 8 immunophenotypes have a causal impact on PsA. Specifically, 7 immune cell traits were found to be positively associated with PsA risk: CD25 on IgD+ CD24+ B cell (OR, 1.26; 95% CI 1.14-1.41; PFDR = 1.24 × 10-3), CD25 on CD24+ CD27+ B cell (OR, 1.25; 95% CI 1.14-1.38; PFDR = 3.12 × 10-4), CD25 on memory B cell (OR, 1.26; 95% CI 1.14-1.38; PFDR = 3.12 × 10-4), CD25 on lgD- CD38- B cell (OR, 1.30; 95% CI 1.16-1.47; PFDR = 1.24 × 10-3), CD25 on unswitched memory B cell (OR, 1.27; 95% CI 1.15-1.40; PFDR = 3.12 × 10-4), T cell absolute cell (OR, 1.70; 95% CI 1.30-2.21; PFDR = 4.72 × 10-3), and lymphocyte absolute cell (OR, 1.99; 95% CI 1.52-2.61; PFDR = 1.56 × 10-4); while only 1 immune cell trait (SSC-A on CD4 + T cell) exhibited a negative correlation with PsA (OR, 0.49; 95% CI 0.38-0.63; PFDR = 1.41 × 10-5). No evidence of heterogeneity or horizontal pleiotropy was observed (P > .05). Besides, PsA did not show a reverse causal effect on immunophenotypes. Our study has elucidated the causal relationship between 731 immune cell traits and PsA, shedding light on the intricate interplay between immune cells and PsA. These findings offer valuable insights for future clinical and basic researches.