The specificity of anti-carbamylated protein antibodies for rheumatoid arthritis in a setting of early arthritis

Abstract

IntroductionAnti-carbamylated protein (anti-CarP) antibodies have been described in rheumatoid arthritis (RA) and arthralgia patients at risk of developing RA. To what extent these autoantibodies are specific for RA is unknown. Therefore, we investigated the diagnostic performance of the presence of anti-CarP antibodies for RA in a setting of early arthritis.MethodsAnti-CarP antibodies were detected using carbamylated fetal calf serum as substrate. Anti-CCP2 antibodies were measured using enzyme-linked immunosorbent assay and immunoglobulin M (IgM) rheumatoid factor (RF) as part of routine care. Sera were derived from patients in the Leiden Early Arthritis Clinic cohort obtained at inclusion. Test characteristics were determined using the fulfillment of the 2010 RA criteria after 1 year as outcome.ResultsIn total 2086 early arthritis patients were studied regarding the presence of anti-CarP antibodies. We observed that the sensitivity and specificity of the presence of anti-CarP antibodies for RA were 44 % and 89 %, respectively. As a reference, sensitivity and specificity of the presence of anti-CCP2 antibodies were 54 % and 96 %, respectively, and of IgM-RF 59 % and 91 %. Patients harboring anti-CarP antibodies not classified as RA were mainly diagnosed with undifferentiated arthritis and less frequently reactive arthritis and psoriatic arthritis.ConclusionAnti-CarP antibodies are predominantly present in RA but can also be detected in other forms of arthritis.

Prevalence, sensitivity and specificity of antibodies against carbamylated proteins in a monocentric cohort of patients with rheumatoid arthritis and other autoimmune rheumatic diseases

“…Recently, Shi et al investigated the diagnostic performance of anti-CarP in RA in a large cohort of patients with early arthritis and demonstrated that these antibodies are predominantly detected in RA, but that a small percentage of patients with almost all forms of early arthritis were also anti-CarP-positive [19]. Considering the high prognostic and predictive value that anti-CarP have demonstrated in patients with RA, the aim of this study was to evaluate their prevalence, sensitivity and specificity in a large monocentric cohort of patients with RA compared to other autoimmune rheumatic diseases (AIRDs).…”

The association between anti-carbamylated protein (anti-CarP) antibodies and radiographic progression in early rheumatoid arthritis: a study exploring replication and the added value to ACPA and rheumatoid factor

“…The present study is the first providing independent replication of the association between anti-CarP antibodies and radiographic progression within the ACPA-negative population in a large cohort of patients with RA with longitudinal radiographs over 8 years. Anti-CarP antibodies are predominantly present in RA with the reported sensitivity and specificity for RA of 44% and 89%, respectively 26. Intriguingly, already in the presymptomatic individuals the presence of anti-CarP antibodies is associated with RA development in ACPA-negative individuals and also with worse radiological progression independent of ACPA 15.…”

The role for neutrophil extracellular traps in cystic fibrosis autoimmunity

“…neutrophil enzymes that localize to NETs induce posttranslational modifications, such as citrullination and carbamylation, thus creating neoantigens that lead to anti-citrullinated protein autoantibodies (ACPA) and anti-carbamylated protein autoantibodies (ACarPA) (22)(23)(24)(25)(26). Given the abundance of nucleic acids in NETs, the induction of autoantibodies by NETosis is likely to be facilitated by TLR 7/9-mediated B cell activation (27).…”