Contraceptive Choices Affect RA-Specific Autoantibodies in Women at Risk for RA

The choice of contraception for women at increased risk of rheumatoid arthritis (RA) may affect detectable levels of autoantibodies, specific to RA, in the blood, a new study has found. Women who had used an intrauterine device (IUD) were almost 3 times more likely to test positive for autoantibodies related to RA.

The diagnosis of rheumatoid arthritis is not based on blood tests alone, but certain tests that measure nonspecific inflammatory markers or disease-specific autoantibodies are helpful in determining an accurate diagnosis. For example, most people with RA will test positive for rheumatoid factor (RF). Those that do not test positive for RF, up to a third of people with RA, may be diagnosed with sero-negative RA.

Autoimmunity in rheumatoid arthritis is often characterized by the presence of autoantibodies directed against citrullinated protein/peptide antigens (ACPAs) specific to RA that are detected with an anti-cyclic citrullinated peptide (anti-CCP) enzyme-linked immunosorbent assay (ELISA) test. In those already diagnosed with RA, the presence of serum ACPAs predicts a more erosive disease course.

ACPAs can also be detected in the serum of healthy individuals years before clinical onset of RA. According to a recent study presented at the annual meeting of the American College of Rheumatology in Boston, MA, the choice of contraception in women at increased risk for RA may affect serum ACPA positivity.

In the Studies of the Etiology of RA (SERA) project, 1243 first degree relatives (FDR) of probands with RA who are enrolled are women. Sonia Khatter, from the University of Colorado School of Medicine in Aurora, and colleagues studied female FDRs who at their baseline visit had serum ELISA testing for ACPA and a contraceptive and pregnancy history taken (n=336). All subjects were free from clinical manifestations (or symptoms) of inflammatory arthritis at the time of serum testing. Only one subject was randomly selected per family, so the final analysis included 297 FDRs.

In this group of women with increased risk of RA, researchers found that after adjustment for age, race, and smoking, prior use of the oral contraceptive pill (OCP) was associated with a decreased risk of serum ACPA positivity (odds ratio, 0.34). These results align with previous studies that found an association between OCP use and decreased risk of rheumatoid factor (RF) positivity. In contrast, researchers found an increased risk for ACPA positivity in women who had a history of intrauterine device (IUD) use (odds ratio, 2.68).

It is not known what mechanisms are in play that link contraceptive factors to the development of ACPAs; however, Khatter et al (2014) note that unlike OCPs, IUDs have been shown to generate endometrial inflammatory responses. Therefore, the association of IUD use and ACPA positivity suggest that IUD-induced endometrial inflammation may be a potential mucosal trigger of RA-related antibodies.

This study revealed no significant correlations between ACPA positivity and pregnancy or breastfeeding. First degree relatives who were ACPA+ were slightly older than those who were ACPA-. The mechanisms by which OCPs could protect against RA and IUD use could increase risk for RA-related autoimmunity warrant further study.

 

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