Isotype distribution of ANTI–CYCLIC citrullinated peptide antibodies in undifferentiated arthritis and rheumatoid arthritis reflects an ongoing immune response

AbstractObjectiveThe evolution of the rheumatoid arthritis (RA)–specific anti–cyclic citrullinated peptide (anti‐CCP) antibody response, as measured by the isotypes of anti‐CCP, has not been described. This study was undertaken to determine anti‐CCP isotype usage in patients with undifferentiated arthritis (UA), patients with recent‐onset RA, and patients with RA of long duration.MethodsIgA, IgM, and IgG subclasses of anti‐CCP were measured by enzyme‐linked immunosorbent assay in serum samples that were obtained from IgG anti‐CCP antibody–positive patients with UA (n = 110) and IgG anti‐CCP antibody–positive patients with RA (n = 152) early after the onset of arthritis. Patients with UA in whom RA developed within 1 year (UA→RA) were compared with patients with UA in whom RA did not develop within 1 year (UA→UA). In addition, baseline serum samples obtained from a subset of patients with RA (n = 64) were compared with sera obtained from the same patients a median of 7 years later.ResultsIgM anti‐CCP was present in early samples from both patients with UA and patients with RA and in followup samples from patients with RA. Several IgG anti‐CCP antibody–positive patients who did not have IgM anti‐CCP early after disease onset did display IgM anti‐CCP later in the course of the arthritis. A diverse pattern of isotype usage was detected in early samples, with a trend toward lower frequencies of all isotypes of anti‐CCP in patients with UA compared with patients with RA and in UA→UA patients compared with UA→RA patients. Levels of all isotypes except IgG1 had decreased after 7 years.ConclusionThese data indicate development of the anti‐CCP isotype repertoire into full usage early in the course of arthritis. The sustained presence of IgM anti‐CCP indicates ongoing recruitment of new B cells into the anti‐CCP response, reflecting a continuous (re)activation of the RA‐specific anti‐CCP response during the course of anti‐CCP–positive arthritis.