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.

The genetic pathogenesis, diagnosis and therapeutic insight of rheumatoid arthritis

“…Destruction of synovial joints might result in severe disability and premature mortality . RA is also characterized by the production and presence of several autoantibodies in the serum and synovial fluid that could present many years prior to the disease onset . Among autoantibodies only rheumatoid factor (RF), antibodies to immunoglobulin binding protein and anti‐citrullinated protein antibody (ACPA) have sufficient sensitivity and specificity to be clinically useful for the diagnosis of RA .…”

IL‐7R gene polymorphisms among patients with rheumatoid arthritis: A case–control study

“…The clinical presentation of RA is characterized by inflammation of the joint synovium, progressive articular destruction, and other comorbidities such as cardiovascular disease, lung disease, infections, and some malignancies (Metsios, Stavropoulos‐Kalinoglou, & Kitas, ), which usually contribute to declining life expectancy, early unemployment, and severe disability even death (Sokka et al, ). The prevalence is about three times higher in women than that in men (Derksen, Huizinga, & van der Woude, ). Clinically, there represents a huge challenge for immediate recognition in early stage of RA.…”

Current and novel anti-inflammatory drug targets for inhibition of cytokines and leucocyte recruitment in rheumatic diseases

“…Genetic and environmental factors promote biological conditions including the formation of autoantibodies such as Rheumatoid factor, and anticitrullinated protein antibodies. It appears these can be detected even before evidence of RA sets in, suggesting there is a sequence of inflammatory events leading to inflamed synovial tissue, articular damage and bone erosion . Along with several factors, continued inflammation, propagated by cytokines such as TNF‐α, increase articular damage resulting in increased release of self‐proteins.…”