Causal relationship between immunophenotypes and rheumatoid arthritis: A 2-sample Mendelian randomization study

As previous studies have demonstrated an association between immune inflammation and rheumatoid arthritis (RA), our study aimed to lend novel insight by exploring the potential causal association between RA and different immunophenotypes. Data were obtained from the genome-wide association study (GWAS) from Finn Gen. The dataset of GWAS contains a cohort of 6236 RA cases and 147,221 controls in European population. Data on immune cell traits are publicly available from the GWAS catalog. A total of 731 immunophenotypes were included in this study including absolute cell counts (ACs), median fluorescence intensity, morphological parameters, and relative cell counts. Mendelian randomization analysis was performed by several methods, and sensitivity analysis and visualization of the results were also carried out. After being adjusted by false discovery rate (FDR), 6 immune phenotypes were significantly and causally associated with the development of RA: CD16 on CD14+ CD16+ monocytes (adjusted odds ratio [OR]: 0.950, 95% confidence interval [CI]: 0.924-0.977, P = 4.04 × 10-4), CD62L-CD86+ myeloid DC %DC (adjusted OR: 1.048, 95% CI: 1.021-1.076, P = 4.29 × 10-4), CD62L-CD86+ myeloid DC AC (adjusted OR: 1.050, 95% CI: 1.024-1.076, P = 1.11 × 10-4), CD62L- myeloid DC AC (adjusted OR: 1.067, 95% CI: 1.033-1.101, P = 8.35 × 10-5), DC AC (adjusted OR: 1.105, 95% CI: 1.062-1.149, P = 7.73 × 10-7), myeloid DC AC (adjusted OR: 1.060, 95% CI: 1.029-1.091, P = 9.96 × 10-5). In addition, we found that CD62L- Dendritic cell % increases with the onset of RA (OR: 1.136, 95% CI: 1.064-1.213, P = 1.36 × 10-4, PFDR = 0.099). This study explored the association between different immunophenotypes and RA, which may lend some novel insights into RA pathogenesis and facilitate the development of new treatments.