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Review
. 2021 Mar 1;23(4):21.
doi: 10.1007/s11926-021-00993-0.

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

Vanessa L Kronzer  1 , John M Davis 3rd  2
Affiliations
Review

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

Vanessa L Kronzer et al. Curr Rheumatol Rep. .

Abstract

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. 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.

Keywords: Epidemiology; Etiology; Genetics; Pathogenesis; Review; Rheumatoid arthritis.

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Conflict of interest statement

Vanessa Kronzer declares that she has no conflicts of interest.

John Davis reports a research grant from Pfizer and has participated on advisory boards for Abbvie and Sanofi-Genzyme, outside the submitted work.

Figures

Fig. 1
Fig. 1
Current research efforts to understand the pathogenesis of RA use either a “top-down” approach, which focuses on pre-RA including anti-posttranslationally modified protein antibodies (AMPAs) and glycosylation, or alternatively a “bottom-up” approach, which focuses on functional genomics
See this image and copyright information in PMC

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