Serum Isthmin-1 Level as a Biomarker of Disease Activity in Rheumatoid Arthritis: Correlation With Musculoskeletal Ultrasound Findings

Rheumatoid arthritis is a chronic autoimmune disease characterized by persistent synovitis, pannus formation, and bone erosion leading to joint damage and functional impairment . It manifests as a symmetrical polyarthritis predominantly affecting the small joints of the hands, the earliest and most severely affected site in RA. A total of 94% of the patients suffered from at least one hand or wrist symptom after 2-4 years of disease duration. The most frequently described symptoms were pain, stiffness of the hand, muscle weakness, paresthesia, and a limited fist, which significantly impair their daily hand function. Current monitoring tools, including ESR, CRP, and DAS-28, lack sensitivity for subclinical synovitis. These limitations underscore the need for novel biomarkers integrating systemic inflammatory activity with joint pathology and functional status.

Isthmin-1 (ISM1), a multifunctional adipokine that suppresses NF-κB pathway, thereby reducing pro-inflammatory cytokine production and promoting tissue repair . This mechanism holds relevance in RA, where aberrant NF-κB activation drives synovitis and Th17-mediated immune responses . Its observed reduction in active RA signifies a loss of endogenous anti-inflammatory counter-regulation, establishing ISM1 as a promising biomarker for disease activity monitoring .

Musculoskeletal ultrasound (MSUS) provides superior sensitivity compared to physical examination for detecting synovitis (. MSUS findings correlate with structural damage and functional decline, making it a valuable tool for monitoring disease impact on hand joints . This study investigates correlations between serum ISM1 levels, MSUS findings, and hand function to identify biological links for novel RA therapies that preserve joint function and enhance quality of life.