Diagnostic accuracy of anti-carbamylated protein antibodies in rheumatoid arthritis: a systematic review and meta-analysis

Abstract

Abstract: Anti-carbamylated protein (anti-CarP) antibodies have emerged as novel serologic markers in rheumatoid arthritis (RA). This meta-analysis aimed to assess the diagnostic accuracy of anti-CarP antibodies in RA patients.A systematic Literature search was conducted through April 2025. Primary outcome was diagnostic accuracy of anti-CarP antibodies compared to healthy controls; secondary outcomes included subgroup analyses by anti-citrullinated protein antibodies (ACPA) status.Thirty-six studies (7431 RA patients; 3347 healthy controls) were included. Most used in-house ELISA platforms. Overall, Anti-CarP antibodies showed high specificity but Limited sensitivity in detecting RA with pooled sensitivity and specificity of 44% (95% CI: 39–49%, I²=91.5%) and 96% (95%CI: 94–97%, I²=65.5%), respectively. The pooled diagnostic odds ratio was 14.72 (95%CI: 10.75–20.15, I2 = 62.1%), and the area under the summary receiver operating characteristic (SROC) curve was 0.825 (95%CI: 0.797–0.854). In subgroup analysis with studies using carbamylated fetal calf serum as targeted antigen (n = 16), sensitivity and specificity were 41% (95%CI: 38–45%, I²=82.3%) and 96% (95%CI: 95–98%, I²=59.6%). In ACPA-negative patients, sensitivity was 24% (95%CI: 18–31%, I²=87.2%), and specificity was 95% (95%CI: 93–97%, I²=70.3%) with the area under the SROC of 0.755 (95%CI: 0.705–0.805). In ACPA-positive patients, sensitivity was 49% (95% CI: 41–57%, I²=94.0%), and specificity was 95% (95%CI: 93–97%, I²=72.0%) with the area under the SROC of 0.855 (95% CI: 0.806–0.904).Anti-CarP antibodies demonstrate high specificity but limited sensitivity for RA diagnosis. PROSPERO registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251065177.