1 article
Rheumatoid arthritis is a systemic autoimmune disease in which persistent synovitis drives joint destruction and disability. Conventional biomarkers such as C-reactive protein and erythrocyte sedimentation rate are widely used to assess disease activity, but they fail to capture inflammation in a considerable proportion of patients and may be confounded by therapies such as interleukin-6 inhibition. Calprotectin (S100A8/A9, MRP8/14), a neutrophil- and monocyte-derived alarmin, has emerged as a potential biomarker reflecting the true inflammatory burden in rheumatoid arthritis. This review aimed to critically appraise the clinical and diagnostic value of calprotectin in adult rheumatoid arthritis, with emphasis on its relationship to disease activity, comparative performance against C-reactive protein and erythrocyte sedimentation rate, methodological aspects of measurement, and role in therapeutic monitoring.
We systematically reviewed studies published between 2010 and 2025 that investigated calprotectin in adult rheumatoid arthritis, focusing on serum, plasma, synovial fluid, and fecal measurements, and their associations with disease activity, imaging, treatment response, and outcomes. Additionally, seminal articles published before 2010 were included when they provided essential historical context or foundational theoretical data relevant to the understanding of calprotectin in rheumatoid arthritis. Pediatric and animal studies were excluded.
Serum calprotectin is consistently elevated in rheumatoid arthritis compared with healthy controls and correlates strongly with swollen joint counts, composite indices, and ultrasound-detected synovitis, often outperforming C-reactive protein and erythrocyte sedimentation rate. Synovial fluid calprotectin is markedly increased, reflecting local production and aggressive synovitis, while fecal calprotectin has limited utility except in cases of concomitant gastrointestinal involvement. Importantly, calprotectin levels remain reliable in patients receiving IL-6 inhibitors, where C-reactive protein is suppressed. High baseline calprotectin predicts radiographic progression and poor functional outcomes, whereas declining levels parallel therapeutic response to DMARDs and biologics. Recent studies suggest calprotectin may help identify patients at risk of relapse during apparent remission, though its predictive value for treatment response to TNF inhibitors appears limited.
Calprotectin is a sensitive biomarker of inflammation in rheumatoid arthritis, offering distinct advantages over traditional acute-phase reactants in detecting residual disease and guiding therapeutic monitoring. Standardization of assays, establishment of validated cut-off values, and large prospective validation studies are required before routine integration into clinical practice.