The role of autoantibodies in the pathophysiology of rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation. The presence of autoantibodies in the sera of RA patients has provided many clues to the underlying disease pathophysiology. Based on the presence of several autoantibodies like rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), anti-carbamylated protein antibodies (anti-CarP), and more recently anti-acetylated protein antibodies RA can be subdivided into seropositive and seronegative disease. The formation of these autoantibodies is associated with both genetic and environmental risk factors for RA, like specific human leukocyte antigen (HLA) alleles and smoking. Autoantibodies can be detected many years before disease onset in a subset of patients, suggesting a sequence of events in which the first autoantibodies develop in predisposed hosts, before an inflammatory response ensues leading to clinically apparent arthritis. Research on the characteristics and effector functions of these autoantibodies might provide more insight in pathophysiological processes underlying arthritis in RA. Recent data suggests that ACPA might play a role in perpetuating inflammation once it has developed. Furthermore, pathophysiological mechanisms have been discovered supporting a direct link between the presence of ACPA and both bone erosions and pain in RA patients. In conclusion, investigating the possible pathogenic potential of autoantibodies might lead to improved understanding of the underlying pathophysiological processes in rheumatoid arthritis.

Keywords: ACPA; Autoantibodies; Pathophysiology; Rheumatoid arthritis.

Fig. 1

Model of the possible role of autoantibodies in disease pathophysiology. Genetic and environmental risk factors might lead to increased rate of posttranslation modification (hypercitrullination, hypercarbamylation). Autoantibodies against these posttranslational modifications are produced (ao ACPA) which can activate other (immune) cells via Fc receptors and stimulate cytokine production. The underlying inflammatory cascade eventually results in clinically apparent arthritis. AMPA anti-modified protein antibodies