Discovery of Novel Antigenic Targets and Autoantibody Markers in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is the most common auto-immune disease characterized by chronic inflammation of synovial joints. The aim of this study was to identify novel target (auto)antigens and antibody biomarkers for early RA patients and RA patients that are seronegative for the 2 diagnostically applied serological RA markers, rheumatoid factor (RF) and anti-CCP (cyclic citrullinated peptides) antibodies (ACPA), by applying an autoantibody profiling procedure based on cDNA phage display. We report the identification of 14 novel target antigens and autoantibody markers for RA. Inclusion of the detection of antibodies against these antigens to the diagnostic testing for RF and ACPA presence increased the sensitivity of serological tests for RA by 25%. Moreover, antibodies against our panel were detected in an early disease phase and were associated with higher inflammatory disease activity, demonstrating the diagnostic and prognostic potential of the panel. Furthermore, we identified several novel antigens with exclusive immunoreactivity in ACPA negative RA patients. An increased expression of several of the identified antigens in RA synovial tissue was demonstrated, providing evidence for a biologically relevant role of the antigen-antibody systems in the RA disease process. In conclusion, the identified markers are proven to be valuable for improved RA diagnosis and prognosis prediction, especially for RA patients that are seronegative based on current diagnostic laboratory tests. Moreover, the identified antigen-antibody systems provide important information regarding underlying disease processes in RA which can ultimately lead to the discovery of novel therapeutic targets.