“…These observations have led to hypotheses that the formation of ACPAs provides a link between the risk factors for RA and the pathway that ultimately leads to clinical arthritis. Notably, smoking can lead to formation of citrullinated proteins in the lung, the presence of ACPAs is associated with lung inflammation in RA, and ACPAs can be measured in sputum not only in those with RA, but even in individuals at risk for RA who do not yet have ACPAs in their serum (34)(35)(36)(37)(38). Periodontitis, which is bidirectionally associated with RA, is driven by the bacterium Porphyromonas gingivalis, which uniquely among oral flora expresses PAD and thus generates local protein citrullination, leading to formation of ACPAs (33,(39)(40)(41).…”