Background/Purpose: This is the first systematic review and meta-analysis to examine the prevalence, the diagnostic and the prognostic value of anti-carbamylated protein (CarP) antibodies in the entire spectrum of rheumatic diseases.

Methods: We systematically searched Medline, Embase, the Cochrane Library, PubMed, Scopus and Web of Science databases for studies published before June 2021. Two investigators independently screened manuscripts to evaluate their eligibility, their quality and to extract the relevant data.

Results: A total of 105 full-text articles and 48 abstracts were respectively included for further analysis. Among those, 127 papers were eligible for inclusion in the quantitative meta-analysis. 50% of the studies reported anti-Carp antibodies measured by in-house or commercial ELISA using carbamylated feta calf serum (car-FCS) as antigen. Anti-car-FCS IgG antibodies were most prevalent in RA patients with a pooled sensitivity of 37.34% (meta-analysis using random, I2=60.52%, p< 0.0001). A great discrepancy was observed when comparing seropositive and seronegative RA, where pooled sensitivity was 50.27% in seropositive compared to 20.18% in seronegative RA. This trend was confirmed in early RA. The pooled sensitivity in other auto-immune rheumatic diseases was between 15-20%, which was similar to the sensitivity of seronegative RA. Patients with non-inflammatory arthritis such as osteoarthritis had pooled sensitivity of 8.3% which was slightly higher than healthy controls (4.6%). The diagnostic performance of anti-CarP antibodies could be determined in RA for both car-FCS and commercial anti-carbamylated protein ELISA. The area under the summary receiver operator characteristic (ROC) curve of both type was similar, 0.668 and 0.68, respectively. Meta-analysis of correlation coefficient was performed by pooling 8 cohorts of RA assessed by anti-car-FCS ELISA and showed a statistical significant correlation with ACPA (p< 0.001). Meta-analysis of association with anti-Carp and risk factors was performed by pooling 9 cohorts of RA patients assessed by anti-car-FCS ELISA and showed a statistical significant association with ever smoker (p< 0.001), RF+ (p< 0.001) and ACPA+ RA patients (p< 0.001).

Conclusion: Anti-Carp antibodies are specifically sensitive in seropositive RA patients and are present with similar sensitivities in seronegative RA and various other inflammatory arthritis such as PsA, SLE and pSS. This could suggest that anti-CarP antibodies may rather reflect a general auto-immune response than a RA-specific immune reaction.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-carbamylated-antibodies-in-autoimmunity-focus-on-their-diagnostic-and-prognostic-value-a-systematic-review-and-meta-analysis/