Autoantibodies to PAD4 and BRAF in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes cartilage and bone destruction. The mechanisms leading to RA are unknown. There is currently no reliable cure for RA. Early treatment can reduce inflammation, joint damage and bone destruction. Thus, early diagnosis of RA is critical. However, definitive diagnosis of RA can be difficult. Immunologic tests that can be performed for the diagnosis of RA include detection of anti citrullinated protein antibodies (ACPAs). However, one third of RA patients have no ACPAs. To identify new autoantibodies in RA, we used the sera of RA patients to screen protein arrays containing 8000 human proteins. We found and validated two major autoantigens: PAD4 (peptidyl arginine deiminase 4) and BRAF (v raf murine sarcoma viral oncogene homolog B1) catalytic domain. We identified peptide targets of anti PAD4 and BRAF autoantibodies. We observed that anti PAD4 are inhibitory whereas anti BRAF stimulate BRAF activity. Anti PAD4 and anti BRAF antibodies may be used to diagnose RA, particularly in the absence of anti citrullinated protein antibodies.