Chapter 14 - Rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a prototypic autoimmune joint disease with a prevalence of 0.5%–1%. While its cause is unknown, it has a significant genetic predisposition, particularly with the major histocompatibility complex (MHC) but also various other genes, and is characterized by the presence of autoantibodies, such as those against immunoglobulins (rheumatoid factor, RF) and critrullinated peptides (ACPA). However, their pathogenetic role is unclear; while their presence is related to more joint damage, this may be primarily driven by the higher disease activity associated particularly with the presence of RF. Environmental risk factors also appear to be involved in eliciting the disease. This is especially seen in various animal models of RA where commensal agents, specific for each model, are involved in triggering disease. The role of T-cells is less well elucidated; the MHC association and other aspects suggest their involvement, but targeting T-cells and their cytokines is not efficacious in RA patients. Thus they presumably have a role particularly in very early stages of RA, possibly even before signs and symptoms occur. On the other hand, inhibition of proinflammatory cytokines like tumor necrosis factor (TNF) and IL-6 is efficacious, as is B-cell depletion and inhibition of Janus kinases (JAKs). Unfortunately, despite the plethora of available therapies, biomarkers predicting efficacy of a specific mode of action in individual patients are still not available. In the future, increased understanding of RA pathogenesis possibly will allow interfering with early disease processes in people at risk and therefore preventive therapies.