Anti-CarP Antibodies Linked to Disability in Patients with Polyarthritis

Anticarbamylated protein (anti-CarP) antibodies are associated with long-term disease activity and disability in patients with inflammatory polyarthritis. Researchers suggest measuring anti-CarP antibodies to identify patients who are negative for anticitrullinated protein antibodies.  Anticarbamylated protein antibodies were recently identified in patients with inflammatory arthritis. So in this study, researchers set out to investigate a possible connection between anticarbamylated protein antibodies and long-term disability outcomes in patients with inflammatory polyarthritis, which they found. The study, of 1,995 patients (66% female) from the Norfolk Arthritis Register (NOAR), included adults with recent-onset swelling of more than two joints for more than four weeks from 1990 to 2009.  The findings as reported in the Oct. 6 online issue of the Annals of the Rheumatic Diseases:  Anti-CarP antibodies were significantly associated with more disability and higher disease activity, HAQ multivariate B-coefficient (95% CI) 0.12 (0.02 to 0.21), an association that was also significant in the ACPA-negative subgroups. There were also some secondary associations of rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA) and anti-CarP antibodies, suggesting that measuring ACPA and anti-CarP could be useful in identifying patients with worse long-term outcomes. Patients with anti-CarP antibodies were more disabled and had higher disease activity early in the disease and they continued to have more functional disability and disease activity as compared to anti-CarP antibody negative patients.  “Given that our results demonstrated an additive effect of each antibody, it may, therefore, be useful to test more than one antibody in clinical practice when trying to assess current and future disability and disease activity,” the researchers wrote. However, as noted in the study, there are currently no commercial assays currently available to test for anti-CarP antibodies, but there are some in development. Recent studies have shown that the presence or absence of autoantibodies can provide prognostic information to clinicians and patients. In addition, rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) are known to be associated with more severe disease activity,  greater levels of disability and increased mortality.  The new analysis shows that anti-CarP antibodies could be an important additional family of antibodies to predict long-term outcomes in patients with inflammatory polyarthritis and, with RF and (ACPA), it could be a useful test. “It was interesting to note in this analysis that the coefficients for ACPA and anti-CarP antibodies were very similar. This suggests that, in terms of disability and disease activity over time, the impact of ACPA and anti-CarP antibodies are similar in patients with IP who test positive for these antibodies,” wrote Suzanne Verstappen, MD, of the University of Manchester in the UK, and colleagues. Anticarbamylated protein (anti-CarP) antibodies “are directed against a post-translational modification of the amino acid lysine to homocitrulline in the presence of cyanate. They have been shown to predate the onset of symptoms, and may occur before or after the development of ACPA. Further, they have been shown to predict development of arthritis in patients with arthralgia. However, it is not yet known if they are associated with long-term disability and disease activity,” researchers wrote.[[{"type":"media","view_mode":"media_crop","fid":"42484","attributes":{"alt":"©Lightspring/Shuttersstock.com","class":"media-image media-image-right","id":"media_crop_6290876083076","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4608","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"","typeof":"foaf:Image"}}]] Even though some patients who test negative for anticitrullinated protein antibodies and rheumatoid factor don’t meet the 2010 RA ARC/EULAR criteria for inflammatory polyarthritis, they do meet the 1987 criteria. “Nevertheless, in clinical practice, there remains a subset of apparently seronegative patients who go on to experience high levels of disease activity and disability. If these patients could be distinguished from those patients with a milder disease course, they could benefit from early aggressive intervention,” the researchers wrote. 

References:

Humphreys JH, Verheul MK, et al. "

Anticarbamylated protein antibodies are associated with long-term disability and increased disease activity in patients with early inflammatory arthritis: 

results from the Norfolk Arthritis Register,"

Annals of the Rheumatic Diseases

. Oct. 6, 2015. http://dx.doi.org/10.1136/annrheumdis-2015-207326