Proteomic mapping of rheumatoid factors in early rheumatoid arthritis

Rheumatoid factors (RFs) are archetypal autoantibodies that have intrigued investigators and provided invaluable insights into the mechanisms of inflammation and immunity. They are targeted against the Fc portion of IgG, are primarily of the IgM isotype, and are found in patients with a myriad of systemic autoimmune and infectious diseases, as well as healthy subjects (1). To date these antibodies have been measured with nephelometric and solid‐phase immunoassays (1); however, these techniques cannot be used to identify the immunoglobulin heavy‐chain variable (Ig VH) regions, which remain one of the most important structures in determining antibody specificity. Recently, we showed that precipitable and soluble RFs can easily be subjected to mass spectrometric (MS) proteomic sequencing in Sjögren’s syndrome (SS) (2) and cryoglobulinemia (3). In the present study we extended this technique to demonstrate, for the first time, the dynamic changes in RF immunoglobulin subfamilies in early rheumatoid arthritis (RA) (diagnosed <12 months from symptom onset) before and after treatment with disease‐modifying antirheumatic drugs (DMARDs) and anti–tumor necrosis factor (TNF) biologic agents.