Causal Relationships between Immune Cells and Rheumatoid Arthritis

Abstract

Abstract Background When it comes to the beginning, course, diagnosis, and management of rheumatoid arthritis (RA), immune cells (ICs) are crucial. However, because of the intricate relationships that exist between RA and the immune system, it is difficult to determine how a particular class or type of immune cell affects RA, and research on this topic is seldom able to rule out the possibility that RA will interfere with the reversal action of ICs. Methods To investigate and screen out the impacts on RA from 731 ICs, we mostly used MR analysis using IVW (inverse variance weighted), Weighted median, and MR-Egger regression methods. Then, the inverse effect of RA on ICs was explored by reversed MR. Finally, MR-Egger intercept, Cochran's Q test, and “Leave-one-out” are conducted to measure the degrees of of pleiotropy and heterogeneity. Results 9 immune phenotypes were found significantly linked to RA risk: IgD- CD27- B cell %B cell (OR = 1.17 95%CI = 1.06–1.29), dendritic cell absolute count (OR = 1.07 95%CI = 1.02–1.13), CD86 + myeloid dendritic cell absolute count (OR = 1.06 95%CI = 1.02–1.11), CD25 on memory B cell (OR = 1.08 95%CI = 1.02–1.13), CD27 on memory B cell(OR = 0.91 95%CI = 0.85–0.98), CD3 on effector memory CD4 + T cell (OR = 0.97 95%CI = 0.94-1.00), CD25 on CD4 + T cell (OR = 0.93 95%CI = 0.87–0.98), CD45 on CD33br HLA DR + CD14dim(OR = 1.04 95%CI = 1.01–1.06), CD11b on CD33br HLA DR + CD14dim(OR = 0.95 95%CI = 0.91–0.99). While only RA on CD25 on memory B cell (OR = 0.95 95%CI = 0.90-1.00) and CD45 on CD33br HLA DR + CD14dim (OR = 0.92 95%CI = 0.87–0.98) were found in reverse MR. Besides, the results of MR-Egger intercept suggest that there exists no evidence of horizontal pleiotropy. Conclusion Our study identified an association between specific immune cells and RA, and this association could guide the future diagnosis and treatment of RA.