Physical Activity Associates With Lower Systemic Inflammatory Gene Expression in Rheumatoid Arthritis
Sarah L. Patterson, Shenghuan Sun, Dmitry Rychkov, Patricia Katz, Alexandra Tsitsiklis, Mary C. Nakamura, Paula Hayakawa Serpa, Charles Langelier, Marina Sirota
Abstract
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: < 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.