RT Journal Article
SR Electronic
T1 Physical Activity Associates With Lower Systemic Inflammatory Gene Expression in Rheumatoid Arthritis
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.220050
DO 10.3899/jrheum.220050
A1 Sarah L.  Patterson
A1 Shenghuan Sun
A1 Dmitry Rychkov
A1 Patricia Katz
A1 Alexandra Tsitsiklis
A1 Mary C.  Nakamura
A1 Paula Hayakawa  Serpa
A1 Charles R  Langelier
A1 Marina Sirota
YR 2022
UL http://www.jrheum.org/content/early/2022/08/28/jrheum.220050.abstract
AB Objective While general population studies have shown inverse associations between physical activity and common inflammatory biomarkers, the effects of physical activity on inflammatory gene expression and signaling pathways in rheumatoid arthritis (RA) remain unknown. We aimed to determine whether physical activity independently associates with expression of inflammatory genes among people with RA. Methods This was a prospective observational study of adults with RA. Physical activity was measured by quantitative actigraphy over 7 consecutive days, and peripheral blood collected during the same time period was used for RNA sequencing followed by differential gene expression, pathway, and network analyses. Results Actigraphy and RNA sequencing data were evaluated in 35 patients. The cohort had a mean age of 56 (SD 12) years, and was 91% female, 31% White, 9% Black, 9% Asian, and 40% Hispanic. We found 767 genes differentially expressed (adjusted P < 0.1) between patients in the greatest vs lowest physical activity tertiles, after adjusting for sex, age, race, and ethnicity. The most active patients exhibited dose-dependent downregulation of several immune signaling pathways implicated in RA pathogenesis. These included CD40, STAT3, TREM-1, interleukin (IL)-17A, IL-8, Toll-like receptor, and interferon (IFN) signaling pathways. Upstream cytokine activation state analysis predicted reduced activation of tumor necrosis factor-α and IFN in the most active group. In sensitivity analyses, we adjusted for RA disease activity and physical function and found consistent results. Conclusion Patients with RA who were more physically active had lower expression of immune signaling pathways implicated in RA pathogenesis, even after adjusting for disease activity, suggesting that physical activity may confer a protective effect in RA.