Anti-citrullinated SR-A Peptide (Anti-csp) Antibody as a Biomarker in Rheumatoid Arthritis (RA).

1. To measure serum level of anticitrullinated SR-A peptide antibody (anti-CSP) in RA patients compared to healthy controls . 2. To assess the diagnostic performance of anti-CSP for RA specifically seronegative RA patients. 3. To evaluate correlation of serum anti-CSP level with disease activity and functional disability scores in RA patients.

Rheumatoid arthritis (RA) is a common a chronic autoimmune disease that can lead to joint destruction, disability, and premature mortality .Early diagnosis is crucial for preventing long-term damage and disability. Anticyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor (RF) are classical serological markers for the diagnosis of RA and have been integrated into the 2010 (ACR/EULAR) classification criteria for RA . However, they show a modest discriminating power. The sensitivity and specificity are 67% and 95% for antiCCP, and 69% and 85% for RF, respectively . Therefore, there is an unmet need to identify prospective diagnostic biomarkers for RA. Several biomarkers have been identified in peripheral blood or synovial fluid of RA patients, including collagen, fibrinogen, vimentin, fibronectin, and α-enolase . Their posttranslational modification, in particular citrullination, is essential for the pathogenesis of RA. These citrullinated autoantigens could stimulate the secretion of autoantibodies, namely, anticitrullinated protein antibodies (ACPAs). •Anti-CCP is one of the most common ACPAs. ACPAs demonstrate arthritogenic potential and perpetuate inflammation in RA through promoting innate immune cells binding ,complement system activation ,neutrophil extracellular traps (NETs) formation ,and osteoclasts activation . Moreover, accumulating experimental evidence revealed the contribution of the glycosylation changes of ACPAs to the systemic inflammation of RA .Several typical glycosylation patterns of ACPAs have also been identified in RA. Macrophage scavenger receptor A (SR-A, CD204, MSR-1, SCARA1) is a kind of classical pattern recognition receptors (PRRs) primarily expressed on macrophages .Besides its role in innate immunity, accumulating evidence also indicated the functional significance of SR-A in adaptive immunity ,In a large-scale multicenter study, soluble SRA demonstrated a sensitivity of 66.41% and specificity of 91.45% for the diagnosis of RA, with positive predictive value (PPV) of 80.19% and negative predictive value (NPV) of 83.94% . Detecting autoantibodies directed against CSP (anti- CSP) could therefore provide a new serological tool for RA diagnosis. These antibodies may not only enhance diagnostic accuracy particularly in patients who are seronegative for conventional markers but also shed light on novel mechanisms in RA pathophysiology