B-103 A Single Centre Experience of Anti-carbamylated Protein Antibody Testing in the Routine Evaluation of Rheumatoid Arthritis
Authors: Novis C L , Nelson H A , Lebiedz-Odrobina D L , Nandakumar V L 
Published: September 2023

Abstract

Background
Rheumatoid arthritis (RA) early diagnosis and treatment can slow disease progression and potentially prevent bone erosion. Anticyclic citrullinated peptide (CCP) IgG and rheumatoid factors (RF) serological testing supports the diagnosis of RA; however, these markers are not detected in about 20% of RA patients. Recently, IgG antibodies against carbamylated proteins (CarP) emerged with implications on preclinical RA diagnosis and disease severity. CarP testing is offered as part of RA panel (CarP, RF and CCP) and as a standalone test in our institution. In this study, we evaluated the contribution of CarP testing for RA diagnosis in our routine clinical practice. Our objectives were 1) to assess the clinical performance of CarP in combination with CCP and/or RF antibodies 2) to understand the association of CarP with disease severity.

Methods
Our cohort included 331 subjects submitted for RA panel serology. Retrospective chart-review revealed 136 clinically defined RA-positive and 195 RA-negative patients. Patients’ sera were tested for CCP, CarP (Inova Diagnostics, San Diego, US) and RF (Roche Diagnostics, Indianapolis, US) antibodies. Clinical performance characteristics were evaluated for CarP individually and in combination with CCP and RF. Disease manifestations (bone damage and synovitis), were correlated with CarP testing.

Results
Single antibody testing for CarP differentiated RA patients from disease-controls with a 27.2% sensitivity, 93.3% specificity, 74.0% positive predictive value and 64.8% negative predictive value. When CarP testing was combined with RF, specificity increased to 95.4%, in combination with CCP it increased to 98.5% and in a triple combination with CCP and RF, specificity increased to 99.5%. The specificity observed in CCP and RF combination (98.5%) was equivalent to CCP and CarP combination or CCP, CarP and RF triple combination. Amongst the RA patients, frequency of bone erosions was slightly greater (P = 0.76) in the presence of CarP positivity (19/37, 51.4%) compared to the presence of CCP (51/107, 47.7%) or RF (50/112, 44.6%) positivity in isolation and/or in combination. Frequency of synovitis was higher in RA patients that tested positive for CarP (20/37, 54.1%) compared to patients who tested positive for CCP (44/107, 41.1%) or RF (43/112, 38.4%). In the seronegative subgroup, 17.2% (5/29) of CCP negative and 14.3% (3/21) of RF negative patients were positive for CarP. Six out of 8 patients in this subgroup displayed bone erosions and/or synovitis. Of the early RA- diagnosed patients (&lt; 6 months of symptom onset), 22.2% (2/9) were CarP positive, of which one patient (11.1%) was seronegative for CCP but positive for RF.

Conclusion
Despite low sensitivity, individual CarP testing offered a specificity comparable to CCP. In combination with CCP and/or RF, CarP displayed a superior specificity compared to any individual testing, however, was inferior to the CCP and RF combination. CarP positivity independently and/or in combination was associated with a severe disease course. These data support the use of CarP in combination with CCP and RF for assessing disease severity but may not be advantageous for initial diagnosis. In CCP or RF seronegative patients, CarP testing may be beneficial in establishing a diagnosis of RA.