Development of anti-citrullinated protein antibody and rheumatoid factor isotypes prior to the onset of rheumatoid arthritis

We and others have previously shown that the development of rheumatoid arthritis (RA) is preceded by IgG anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) [ 1 , 2 ]. Furthermore, it was shown that other isotypes of ACPA (IgA and, to a lesser extent, the IgM isotype) also predate the onset of RA [ 3 ]. Moreover, smoking has been linked to the development of IgA ACPA in the preclinical phase [ 3 ].