Circulating Calprotectin (cCLP) in autoimmune diseases

Background and aim: Calprotectin (CLP) is a heterodimeric complex formed by two S100 proteins (S100A8/A9), which plays a pivotal role in innate immunity. Due to its intrinsic cytotoxic and proinflammatory properties, CLP controls cell differentiation, proliferation and NETosis and has been associated with a wide range of rheumatic diseases. Our review summarizes the widespread interest in circulating CLP (cCLP) as a biomarker of neutrophil-related inflammation, in autoimmune rheumatic disease (ARD) and non-ARD. Methods: A thorough literature review was performed using PubMed and EMBASE databases searching for circulating calprotectin and synonyms S100A8/A9, myeloid-related protein 8/14 (MRP8/MRP14), calgranulin A/B and L1 protein in addition to specific ARDs and autoimmune non-rheumatic diseases. We selected only English-language articles and excluded abstracts without the main text. Results: High cCLP serum levels are associated with worse structural outcomes in rheumatoid arthritis and to a lesser extent, in spondyloarthritis. In addition, cCLP can predict disease relapse in some autoimmune diseases including systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV) and some severe manifestations of connective tissue diseases, such as glomerulonephritis in SLE, AAV, juvenile idiopathic arthritis, adult-onset Still's disease and lung fibrosis in systemic sclerosis. Therefore, cCLP levels enable the identification of patients who need an accurate and tight follow-up. The clinical usefulness of cCLP as an inflammatory marker has been suggested for inflammatory/autoimmune non-rheumatic diseases, and especially for the monitoring of the inflammatory bowel diseases patients. Currently, there are only a few studies that evaluated the cCLP efficacy as a clinical biomarker in inflammatory/ autoimmune non-rheumatic diseases with controversial results. Future studies are warranted to better clarify the role of cCLP in relation to the disease severity in myasthenia gravis, multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, Graves' orbitopathy, autoimmune bullous diseases and uveitis. Conclusion: Our literature review supports a relevant role of cCLP as potential prognostic biomarker mirroring local or systemic inflammation, especially in chronic inflammatory rheumatic diseases.