Role of the lung in individuals at risk of rheumatoid arthritis

Antibody-positive (seropositive) rheumatoid arthritis (RA) is a complex multiphasic disease developing in genetically susceptible individuals following environmental challenges (such as smoking). RA-associated autoantibodies can develop several years before any clinical signs of joint inflammation, suggesting that triggering of this autoimmunity occurs outside the joints. Epidemiological, clinical, and molecular studies in seropositive individuals at risk for developing RA as well as in early untreated RA suggest a potential role for mucosal sites (especially lung mucosa) as RA-associated autoimmunity trigger sites. This chapter summarizes clinical and molecular studies supporting the lung as a central site for autoimmunity initiation in RA.