Identification of immune complex antigens that are detected prior to early rheumatoid arthritis symptoms and increase with disease progression: Comprehensive serum immune complexome analysis to identify candidate disease biomarkers in health checkup cohort study

Although anti-cyclic citrullinated peptide is a biomarker, its contribution to rheumatoid arthritis pathogenesis is unknown, and it has not been a therapeutic target to date. As inflammatory pathology is present from an early stage, and increased immune complexes have been suggested to contribute to pathogenesis, we investigated the presence of disease-related antigens that form immune complexes that increase in abundance with disease progression. Using immune complexome analysis, we analyzed immune complex antigen to disease progression for very-early rheumatoid arthritis (n = 52) and early rheumatoid arthritis (n = 19), in comparison with healthy controls (n = 28). Very-early rheumatoid arthritis was defined as those positive for anti-cyclic citrullinated peptide antibody who did not fulfill the diagnostic criteria for rheumatoid arthritis. Seven antigens increased with disease progression and were detected at significantly higher abundance in early rheumatoid arthritis than in other major autoimmune diseases. Among these, three antigens have previously reported associations with rheumatoid arthritis pathogenesis.