Background/Purpose:

Anti-carbamylated protein (anti-CarP) antibodies have been described as a new type of autoantibodies specific of patients with rheumatoid arthritis (RA). They seem useful as a new biomarker of disease severity with independence of anti-CCP antibodies (1). In addition, they could also be a biomarker of future development of RA, at least, among patients with arthralgia (2). The aim of this study was to explore the predictive value of anti-CarP antibodies in early arthritis (EA) patients. Identification of the subgroup of EA at high risk of developing RA is a priority for prevention of joint damage and achievement of long-term remission.

Methods:

All the EA patients from a dedicated clinic with a minimum follow-up of two years have been included. These patients were recruited if they have shown 2 or more swollen joints for at least 4 weeks and symptoms for less than a year. Classifiation as RA was done according with the 1987 ACR criteria. Baseline sera from 552 EA patients were analyzed for anti-CarP fetal calf serum (FCS) antibodies by ELISA. Anti-CarP titre was obtained after subtracting reactivity to native FCS from the reactivity to carbamylated FCS. We used as a cut-off the 95 % percentil of 208 healthy donors.

Results:

Near half of the 552 patients (45.6%) fulfilled RA criteria at the end of the 2 years of follow-up. Baseline anti-CarP was 53.4% sensitive and 79.5% specific for RA at study end. These antibodies were found in 65.0% of the RA patients, which is similar to the percentage found in established RA. Presence of anti-CarP was significantly correlated with anti-CCP antibodies and with RF status. However, we observed that 13.0% of the anti-CCP negative RA patients tested positive for anti-CarP antibodies. Baseline anti-CCP and RF combination resulted in 91.9% positive predictive value (PPV) and a 79.6% negative predictive value (NPV) for RA. These values did not change by the addition of anti-CarP antibodies (91.5 and 81.6 %, respectively). In the anti-CCP negative RA patients, anti-CarP antibodies were 49.2% sensitive and 64.4% specific, and their combination with RF antibodies increased only modestly the PPV (from 36.3 with RF to 47.6% with the combination) withouth changing the NPV for RA (from 79.6% to 81.6%). Analysis of the 66 incident RA patients (fullfiling RA criteria by 2 years, but not at baseline) showed similar PPV and NPV with the inclusion of anti-CarP to the obtained with RF and anti-CCP antibodies alone (PPV = 70.6 with the three antibodies, and 72.9 with anti-CCP and RF, and NPV 90.9% in the two analyses). No association was found between anti-CarP status and smoking or DAS28 values.

Conclusion:

Anti-CarP antibodies were present in EA patients and their presence was associated with RA, both prevalent  RA at baseline and incident RA during follow-up. However, they did not add to the prediction of RA available with the already known antibodies except for a modest increase in PPV among the anti-CCP negative patients.

1. Shi J, et al. Proc.Natl.Acad.Sci.U.S.A 2011; 108:17372-7.

2. Shi, J., et al. Arthritis Rheum. 2013; 65(4): 911-5

Supported by grants PI15/01651 and RD12/0009/0008 of the Instituto de Salud Carlos III (Spain) that are partially financed by the European Regional Development Fund of the European Union

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/predictive-value-of-anti-carbamylated-protein-antibodies-in-patients-with-early-arthritis/