Autoantibody Repertoire in Rheumatoid Arthritis: Advances, Challenges, and Clinical Perspectives

Abstract

This narrative review summarizes current evidence on the autoantibody repertoire in rheumatoid arthritis (RA) and its clinical relevance. Autoantibody testing remains central to diagnosis and disease classification, with rheumatoid factor (RF) and antibodies to citrullinated proteins representing the most widely used serological markers. However, these conventional biomarkers do not fully capture the heterogeneity of the disease, and a substantial proportion of patients remain seronegative. In recent years, several emerging autoantibodies, including anti-carbamylated protein antibodies, anti-peptidylarginine deiminase 4 antibodies, anti-RA33, and anti-14-3-3η, have shown potential value as complementary biomarkers, particularly in early or seronegative disease. Some autoantibodies may also be detectable before the onset of clinically apparent arthritis, supporting a possible role in risk assessment and disease stratification. At the same time, their broader clinical application remains limited by assay heterogeneity, non-uniform diagnostic thresholds, and insufficient prospective validation. Overall, established and emerging autoantibodies provide important insight into diagnosis and disease subsets in RA, but further standardization is needed before wider clinical implementation. Cite this article as: He L, Luo Q, Yan J, Lin F. Autoantibody Repertoire in Rheumatoid Arthritis: Advances, Challenges, and Clinical Perspectives. ArchRheumatol. Published online September 16, 2026. doi: 10.5152/ArchRheumatol.2026.26410.