Autoantibodies represent a hallmark of
rheumatoid arthritis (RA), with the
rheumatoid factor (RF) and
antibodies against citrullinated
proteins (ACPA) being the most acknowledged ones. RA patients who are positive for RF and/or ACPA ("seropositive") in general display a different etiology and disease course compared to so-called "seronegative" patients. Still, the seronegative patient population is very heterogeneous and not well characterized. Due to the identification of new
autoantibodies and advancements in the diagnosis of
rheumatic diseases in the last years, the group of seronegative patients is constantly shrinking. Aside from
antibodies towards various post-translational modifications, recent studies describe
autoantibodies targeting some native
proteins, further broadening the spectrum of recognized
antigens. Next to the detection of new
autoantibody groups, much research has been done to answer the question if and how
autoantibodies contribute to the pathogenesis of RA. Since
autoantibodies can be detected years prior to RA onset, it is a matter of debate whether their presence alone is sufficient to trigger the disease. Nevertheless, there is gathering evidence of direct
autoantibody effector functions, such as stimulation of osteoclastogenesis and synovial fibroblast migration in in vitro experiments. In addition,
autoantibody positive patients display a worse
clinical course and stronger radiographic progression. In this review, we discuss current findings regarding different
autoantibody types, the underlying disease-driving mechanisms, the role of Fab and Fc glycosylation and clinical implications.