Abstract
BackgroundCalprotectin (S100A8/S100A9 protein) is known as a damage-associated molecular pattern (DAMP) protein and reflects mainly neutrophil activation. Serum calprotectin levels might be a good alternative to acute-phase protein as a biomarker in inflammatory rheumatic diseases. The aim of this study is to investigate the association of serum calprotectin with disease activity and severity in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA).MethodsSerum calprotectin was measured in patients with RA, axSpA, and PsA from the prospective Swiss Clinical Quality Management (SCQM) registry. Asymptomatic first-degree relatives of RA patients were used as healthy controls (HC). Outcomes included swollen joint count (SJC), Disease Activity Score (DAS), Health Assessment questionnaire (HAQ), joint radiographs, and ultrasound power Doppler (USPD) score for RA; Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS) and coxitis for axSpA; and SJC and Disease Activity Index for PSoriatic Arthritis (DAPSA) for PsA. Comparison of outcomes by calprotectin quartile levels was performed using Kruskal-Wallis tests for continuous outcomes or trend tests for categorical outcomes.ResultsA total of 1729 subjects [RA = 969, axSpA = 451, PsA = 237, and HC = 72] were included. Median levels of serum calprotectin were higher in each disease group compared to HC (p < 0.01). In RA patients, all clinical outcomes were statistically different between quartiles of serum calprotectin, indicating an association between calprotectin levels and higher disease activity (SJC, DAS, and USPD scores) and severity (joint radiographs and HAQ). In axSpA, an association between calprotectin levels and ASDAS score (p < 0.01) and prevalence of coxitis (p = 0.02) was observed. For PsA patients, SJC and DAPSA did not differ across calprotectin quartiles.ConclusionsThis large study supports the association of serum calprotectin levels with disease activity in both RA and axSpA, but not in PsA.
Highlights
Calprotectin (S100A8/S100A9 protein) is known as a damage-associated molecular pattern (DAMP) protein and reflects mainly neutrophil activation
We examined the cut-off for the serum calprotectin level as marker for disease activity with a receiver operating characteristic (ROC) analysis
Our results suggest that calprotectin could be a useful biomarker for monitoring disease activity in rheumatoid arthritis (RA) patients and may add additional information to that provided by C-reactive protein (CRP)
Summary
Calprotectin (S100A8/S100A9 protein) is known as a damage-associated molecular pattern (DAMP) protein and reflects mainly neutrophil activation. The aim of this study is to investigate the association of serum calprotectin with disease activity and severity in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA). Calprotectin is a heterodimeric complex of two non-covalently associated calcium-binding proteins, S100A8 and S100A9 They belong to the S100 proteins family which regroups 25 members [5]. These two proteins are known as myeloid-related protein (MRP) 8 and 14 or calgranulin A and B Debated, it seems that they are functionally active when present in their heterodimeric form [6], forming the calprotectin complex (S100A8/S100A9). Calprotectin is stored in large amounts in the granulocyte cytosol (40–60% of cytosolic protein content) and has both intracellular and extracellular functions Inside the cells, it regulates calcium homeostasis, interacts with the cytoskeleton and microtubules and plays a role in intracellular trafficking of phagocytes. Calprotectin functions as a damage-associated pattern molecules (DAMP) or alarmin, promoting the inflammatory response
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