For patients with rheumatoid arthritis (RA), rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) demonstrate different isotype patterns during disease development, according to results published in Arthritis & Rheumatology.

The study included participants with RA (n=214) and matched control participants (n=210) from the Department of Defense Serum Repository. The researchers tested a mean of 3 pre-RA and 1 post-RA serum samples for RF and ACPA immunoglobulin (Ig) A, IgG, and IgM. They then evaluated the timing and trajectories of autoantibody elevations.

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Compared with control individuals, participants with RA had significant differences in RF-IgA levels at a median of 14.2 years before diagnosis (P <.01). Differences in RF-IgG occurred at 5.0 years, and differences in RF-IgM levels occurred at 7.2 years (both P <.01).

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Participants with RA had significantly different levels of ACPA IgG at 17.9 years before RA diagnosis compared with control individuals (P <.01). For ACPA-IgA, the difference occurred at 6.2 years, and for ACPA-IgM, it differed at 5.0 years (both P <.01).

After RA diagnosis, the only autoantibody that had a significant positivity increase was ACPA-IgA (19% 0-2 years pre-RA vs. 39% >2 years post-RA, P =.04).

The results indicated that among participants with RA, all autoantibodies followed a similar trajectory, with an early initial elevation, a period of stability, and an immediate increase pre-RA diagnosis.

The study included several limitations. The researchers noted that the military cohort used in the study may have a more severe form of RA than other populations. In addition, delays in seeking treatment may mean that the actual time of synovitis onset is earlier than the date of diagnosis.

“These findings have implications for understanding the pathophysiology of disease development,” the researchers wrote.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Kelmenson LB, Wagner BD, McNair BK, et al. Timing of elevations of autoantibody isotypes in rheumatoid arthritis prior to disease diagnosis [published online August 29, 2019]. Arthritis Rheumatol. doi:10.1002/art.41091