Physical Activity Moderates Inflammatory Gene Expression in Rheumatoid Arthritis

Abstract

AbstractBackgroundWhile general population studies have shown associations between greater physical activity and lower inflammatory markers, effects of physical activity on inflammatory pathways in rheumatoid arthritis (RA) remain unknown. We aimed to determine whether physical activity independently associates with differential expression of inflammatory genes in RA.MethodsData derived from an observational RA cohort. Physical activity was measured with the GT9X ActiGraph Link device. RNA extraction from peripheral blood, sequencing library preparation and transcriptomic analyses were performed using established methods. Genes differentially expressed in the most versus least physically active groups (top versus bottom activity tertiles) were identified using DESeq2 after adjusting for sex, age, race/ethnicity, and disease activity. Ingenuity Pathway Analysis (IPA) was employed to identify canonical biological pathways and upstream regulating cytokines associated with physical activity.Results35 participants were enrolled (mean age 56±12 years; 91% female; race/ethnicity 31% white, 9% African American, 9% Asian, 40% Hispanic). 767 genes were differentially expressed (padj<0.1) between high versus low activity groups. The high activity group exhibited downregulation of innate and adaptive immune signaling pathways, including CD40, STAT3, TREM-1, IL-17a, IL-8, toll-like receptor and interferon signaling. Upstream cytokine analysis demonstrated inhibition of TNF-alpha and interferon among individuals in the most active group.ConclusionIn a racially diverse RA cohort, patients who were more physically active had lower expression of immune signaling pathways implicated in RA pathogenesis, even after adjusting for disease activity, suggesting a potential protective effect of physical activity in RA.