Rheumatoid arthritis (RA) is a chronic inflammatory disease resulting from the complex interaction between genes and environment. In a large majority of patients this interaction leads to formation of anti-citrullinated proteins antibodies (ACPA), highly specific for RA. New insights in the early stages of disease development revealed a central role for ACPA immunity outside the joints and already before disease onset in the lungs, the gingival tissue and lymph nodes.
In recent years most knowledge has been gained into the link between the lungs and the joints, suggesting a stepwise development of the disease, initiating in the lungs and ending up in the joints. According to this model smoking induces subclinical inflammation in the lungs, leading to increased local peptide citrullination and formation of ACPA in genetically susceptible individuals. These antibodies will than circulate in the blood of yet healthy individuals to finally localized in the joint when a yet unidentified second hit will promote citrullination of peptides identical to those existing in the lungs. These findings point to an early lung involvement in RA as a potential primary initiation site of the ACPA response.
Disclosure of Interest None Declared