Background/Purpose: Anti-carbamylated protein antibodies (anti-CarP Ab) are emerging serologic markers in rheumatoid arthritis (RA). Anti-CarP Ab has a controversial diagnostic utility in RA but may be particularly useful in patients who are negative for traditional markers such as rheumatoid factor and anti-citrullinated protein antibodies (ACPA). This study aimed to evaluate the diagnostic accuracy of anti-CarP Ab in RA patients with both ACPA-negative (ACPA-) and ACPA-positive (ACPA+) subgroups.

Methods: We systematically searched MEDLINE, Scopus, Web of Science and the Cochrane Library through April 2025. Studies reporting sensitivity and specificity of anti-CarP Ab testing in established RA patients were included. The primary outcome was diagnostic accuracy compared to healthy controls. Secondary outcomes included subgroup analyses of ACPA- and ACPA+ patients.

Results: Thirty-six studies comprising 7431 RA patients and 3347 healthy controls were included. Most used in-house ELISA platforms; fetal calf serum (FCS) was the most common antigen, and IgG was the predominant isotype for detection. Primary outcomes: Anti-CarP Ab showed high accuracy as a diagnostic tool 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 positive likelihood ratio was 9.27 (95% CI: 7.17–11.36, I² = 99.3%), negative likelihood ratio was 0.62 (95% CI: 0.55–0.68, I² = 0.0%), and diagnostic odds ratio (DOR) was 14.72 (95% CI: 10.75–20.15, I² = 62.1%). The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) was 0.825. Subgroup analysis among studies using FCS (n = 16) showed pooled sensitivity of 41% (95% CI: 38-45%, I² = 82.3%) and specificity of 96% (95% CI: 95-98%, I² = 59.6%). In studies detecting IgG only (n =19), sensitivity was 43% (95% CI: 38-48%, I² = 92.8%) and specificity was 96% (95% CI: 94-98%, I² = 60.7%). Secondary outcomes: ACPA- group: pooled sensitivity and specificity were 24% (95% CI: 18-31%, I² = 87.2%) and 95% (95% CI: 93-97%, I² = 70.3%). DOR was 5.29 (95% CI: 3.64-7.67, I² = 41.3%) and AUC of SROC was 0.755 ACPA+ group: pooled sensitivity and specificity were 49% (95% CI: 41-57%, I² 94.0%) and 95% (95% CI: 93-97%, I² = 72.0%). DOR was 18.38 (95% CI: 10.36-32.61, I² = 82.0%) and AUC of SROC was 0.855.

Conclusion: Anti-CarP Ab demonstrates high specificity but low sensitivity for RA diagnosis. Anti-CarP Ab is recommended as a complementary diagnostic tool, particularly in patients who are negative for ACPA.

Figure 1. PRISMA Flow Diagram of Studies Included In the Meta-analysis

Table 2. Diagnostic Accuracy of Anti-carbamylated Protien Antibodies in Rheumatoid Arthritis Patients

Figure 3. Summary Receiver Operating Characteristic Curve of Anti-carbamylated Protien Antibodies

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/diagnostic-accuracy-of-anti-carbamylated-protein-antibodies-in-rheumatoid-arthritis-a-systematic-review-and-meta-analysis/