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Anti-carbamylated protein antibodies: are they useful for the diagnosis of rheumatoid arthritis?

Author

Clin Exp Rheumatol. 2020 Jun 30.Online ahead of print.

Frederique Ponchel 1, Myrthe A M van Delft 2, Xuanxiao Xie 3, Agata N Burska 3, Laurence Duquenne 3, Leendert A Trouw 4, Paul Emery 5

Author Information

1 Leeds Institute of Rheumatic and Musculoskeletal Medicine, The University of Leeds, UK. mmefp@leeds.ac.uk, f.ponchel@leeds.ac.uk.

2 Department of Rheumatology, Leiden University Medical Centre, Leiden University, The Netherlands.

3 Leeds Institute of Rheumatic and Musculoskeletal Medicine, The University of Leeds, UK.

4 Department of Rheumatology, Leiden University Medical Centre, Leiden University; and Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, The Netherlands.

5 Leeds Institute of Rheumatic and Musculoskeletal Medicine, The University of Leeds; and NIHR Leeds Musculoskeletal Biomedical Research Centre, The Leeds Trust Teaching Hospital, Leeds, UK.

Abstract

Objectives: ACR/EULAR-2010 classification criteria for rheumatoid arthritis (RA) rely heavily on the presence of anti-citrullinated peptide antibody (ACPA). The role of anti-carbamylated protein antibodies (anti-CarP) in this context is uncertain. We aimed to investigate the value of anti-CarP for RA classification in patients with early inflammatory arthritis.

Methods: Patients (n=402) were recruited from an early arthritis clinic and followed for 24 months. Healthy controls (n=95) were included. An anti-CarP ELISA was performed (aU/mL). Statistical analysis used regression and AUC analysis.

Results: The criteria for RA were met by 195/402 patients at inclusion; 28 developed RA during follow-up and 179 had other diagnosis (non-RA). 97/195 (49%) RA patients were anti-CarP+ (median 250 uA/mL [IQR 25-762]). In the group that progressed to RA, 7/28 (25%) were positive (82 uA/mL [13-235]) compared to non-RA (p=0.001) with 13/179 (7%) positive (26 uA/mL [5-80]). Being anti-CarP+ alone was observed in 17 patients of whom 7 (41%) were RA. Levels/positivity were not associated with other parameters. Anti-CarP+ had an odds ratio (OR) 6.5 for predicting RA (OR=17.1 for ACPA+ and OR=2.5 for RF+). In ACPA- patients, anti-CarP+ was also predictive of RA (OR=2.39). Being ACPA+/anti-CarP+/RF+ had a high predictive value for RA (OR=29.9 sensitivity/specificity (sen/spe) 33%/99%, positive/negative predictive values (ppv/npv) 97%/54%), however, being ACPA+/anti-CarP+ was superior (OR=36.1 sen/spe=41%/99%, ppv/npv=98%/57%) while being ACPA+/RF+ was inferior (OR=11.9, sen/spe=54%/95%, ppv/npv=94%/62%).

Conclusions: For RA classification, anti-CarP+ was less sensitive than ACPA, but more specific than RF. Anti-CarP+ may prove useful, classifying early arthritis patients, notably ACPA- patients.