Anti-carbamylated protein antibodies are present prior to rheumatoid arthritis and are associated with its future diagnosis

Abstract

Objective: Anti-carbamylated protein (anti-CarP) antibodies could further elucidate early rheumatoid arthritis (RA) pathogenesis and predict clinical disease. We compared the diagnostic accuracy of anti-CarP antibodies for future RA to other RA-related antibodies in military personnel.

Methods: Stored pre-RA diagnosis serum samples from 76 RA cases were tested for anti-CarP fetal calf serum (FCS), anti-CarP fibrinogen (Fib), anticyclic citrullinated peptide antibodies version 2 (anti-CCP2), rheumatoid factor-nephelometry (RF-Neph), and RF isotypes [immunoglobulin M (IgM), IgG, and IgA]. Positivity for all antibodies was determined as ≥ 2 SD of log-transformed means from controls. Relationships between autoantibodies and future RA were assessed in prediagnosis serum for all RA cases compared to controls using sensitivity, specificity, and logistic regression. Differences in diagnostic accuracy between antibody combinations were assessed using comparisons of area under the curves (AUC).

Results: Anti-CarP-FCS was 26% sensitive and 95% specific for future RA, whereas anti-CarP-Fib was 16% sensitive and 95% specific for future RA. Anti-CarP-FCS positivity was associated with future RA, while anti-CarP-Fib trended toward association. The antibody combination of anti-CCP2 and/or ≥ 2 RF (RF-Neph and/or RF-isotypes) resulted in an AUC of 0.72 for future RA, where the AUC was 0.71 with the addition of anti-CarP-FCS to this prior combination.

Conclusion: Adding anti-CarP-FCS to antibody combinations did not improve AUC. However, anti-CarP-FCS was associated with future onset of RA, and was present in prediagnosis serum in ∼10% of RA cases negative for anti-CCP2 but positive for RF.

Keywords: AUTOANTIBODIES; EPIDEMIOLOGY; RHEUMATOID ARTHRITIS.

Figure 1

Trends in the mean levels of anti-CarP-FCS, anti-CarP-Fib, RF-Neph, and anti-CCP2 between RA cases and controls during the prediagnosis period. Arrows indicate where the mean levels between cases and controls are significantly different in the prediagnosis period.