Abstract
BackgroundAntibodies against carbamylated proteins (anti-CarP) have been recently identified in the sera of patients with rheumatoid arthritis (RA). The objective of the study was to evaluate the prevalence, sensitivity and specificity of anti-CarP compared to anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF), replicating the existing data in a large cohort of Italian patients with RA and extending the evaluation to other autoimmune rheumatic diseases (AIRDs).MethodsSerum samples (n = 607) from 309 patients with RA, 200 disease controls and 98 normal healthy subjects (NHS) were evaluated. Anti-CarP were detected using carbamylated fetal calf serum as the antigen. ACPAs were detected using second-generation ELISA and IgM RF was assessed as part of routine analysis.ResultsAnti-CarP antibodies were detected in 117 patients with RA (34.4%), ACPA in 190 patients (61.4%) and RF in 202 patients (65.3%). Two (2.04%) of the NHS were positive for anti-CarP, one NHS (1.02%) was positive for ACPA and three NHS were positive for RF (3.06%). Among disease controls, anti-CarP antibodies were detected in 33 patients (16.5%), ACPA in 29 patients (14.5%) and RF in 64 patients (32%). In particular, 16.8% of patients with systemic lupus erythematosus and 31.1% of patients with Sjögren syndrome were positive for anti-CarP. The sensitivity of anti-CarP, ACPA and RF was 46.8%, 61.8% and 64.4%, respectively and specificity was 91.95%, 89.93% and 76.51%, respectively.ConclusionsThe present study extends the knowledge of anti-CarP antibodies, confirming previous data on the diagnostic accuracy of anti-CarP in RA in a large cohort of Italian patients. Anti-CarP antibodies demonstrated relatively low sensitivity and slightly higher specificity compared to ACPA and RF. Even if predominantly present in RA, anti-CarP was detected in a variable percentage of patients with other autoimmune rheumatic diseases and their generation could be attributed to the inflammatory status; the clinical relevance of anti-CarP antibodies in these latter patients should be further determined.
Highlights
Antibodies against carbamylated proteins have been recently identified in the sera of patients with rheumatoid arthritis (RA)
Patient populations We evaluated a total of 607 frozen stored serum samples from 309 patients with established RA diagnosed according to the 2010 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) criteria, and 200 unselected patients with other diseases [systemic lupus erythematosus (SLE), Sjögren syndrome (SS), systemic sclerosis (SSc), and postmenopausal osteoporosis (OP)], who were not matched by gender or age with the RA group, and who were attending outpatient clinics at Sapienza University of Rome
For the first time we investigated in a single study the positivity of anti-CarP, even including patients with different systemic autoimmune rheumatic diseases (AIRDs), which are known to be associated with the production of several autoantibodies
Summary
Antibodies against carbamylated proteins (anti-CarP) have been recently identified in the sera of patients with rheumatoid arthritis (RA). The objective of the study was to evaluate the prevalence, sensitivity and specificity of antiCarP compared to anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF), replicating the existing data in a large cohort of Italian patients with RA and extending the evaluation to other autoimmune rheumatic diseases (AIRDs). Beside the well-known rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) have been reported to be a very useful diagnostic and prognostic marker of RA [2]. A new autoantibody system recognising antibodies against carbamylated proteins (anti-CarP) has been described [6] but has not yet been implemented for commercial use
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