Etiologies of Rheumatoid Arthritis: Update on Mucosal, Genetic, and Cellular Pathogenesis

PURPOSE OF REVIEW: Over the last few years, the scientific community has made significant progress in understanding the etiology of rheumatoid arthritis (RA). In this review, we summarize those key findings and trends. RECENT FINDINGS: New data strongly implicates respiratory exposures, obesity, diet and microbiome, genetics, and their interactions in the etiology of RA. Furthermore, anti-posttranslationally modified protein antibodies (AMPAs) and abnormal glycosylation may be additional biomarkers for RA. Finally, functional genomics techniques implicate loss of certain macrophage populations and proliferation of synovial fibroblasts in RA. SUMMARY: These findings support the notion that RA originates at mucosal sites, augmented by genetic predisposition, and mediated by certain cell types including macrophages and fibroblasts. Weight loss, physical activity, and diet are additional modifiable factors beyond smoking cessation that can reduce risk of RA. Future epidemiologic and translational studies leveraging multi-omics approaches will help map the precise sequence of events in RA pathogenesis.