Rheumatoid Arthritis: Transition from Systemic Autoimmunity to Joint Inflammation and Bone Loss

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease resulting from the complex interaction between genetic and environmental factors, with at least two distinct clinical phenotypes that are differentiated by the presence or absence of anti-citrullinated protein antibodies (ACPAs), i.e., ACPA-positive RA and ACPA-negative RA (Klareskog et al. 2009). These two phenotypes differ both in terms of risk factors and disease mechanisms. Specific environment-gene interactions (such as smoking and presence of the HLA-DRB1 risk allele variants) only confer risk for developing of ACPA-positive RA but not ACPA-negative RA. ACPA-positive RA has a more severe disease course, and more frequently associates with bone destruction as compared to ACPA-negative RA. More recent findings suggest that ACPA might play an important role in the transition from systemic autoimmunity (that develops before joint inflammation) to joint disease through specific targeting of the bone and activation of osteoclasts. The current chapter will review existing evidence showing that ACPA might be generated at extra-articular mucosal sites and contribute to the initiation of chronic joint inflammation.