Anti-carbamylated protein antibodies in ACCP-negative and ACCP-positive patients with rheumatoid arthritis

Abstract

Objective. Assess the level of antibodies to carbamylated proteins (anti-CarP) and analyse the clinical and immunological associations in patients with ACCP-negative and ACCP-positive variants of rheumatoid arthritis.Materials and methods. 150 patients with a reliable diagnosis of rheumatoid arthritis and 25 patients as healthy controls were included in the study. Depending on ACCP values, two groups of patients were recruited: ACCP-positive (n=75) and ACCP-negative (n=75). RA activity was assessed by the DAS28 (Disease Activity Score 28) index. Determination of antibodies to carbamylated proteins was performed by enzyme-linked immunosorbent assay (BlueGene Biotech, China). Quantitative determination of ACCP in serum was performed by enzyme immunoassay using a commercial reagent kit (AxisShield, UK; upper limit of normal 5.0 U/ml; Orgentec, Germany; upper limit of normal 20.0 U/ml).Results and discussion. Me for anti-CarP in patients with RA was 126.2 [100.83; 157.41] ng/ml and was statistically significantly higher (p<0.001) than healthy controls 88.89 [70.53; 107.75] ng/ml. Among all patients with RA, 50 (33.3%) were anti-Carp positive, 22 (29.3%) were anti-Carp(+) in the ACCP(+) group, 28 (37.3%) in the ACCP(–) group, and 1 (2%) volunteer from healthy controls (p=0.002). In ROC analysis to assess the diagnostic significance of anti-Carp for RA for all patients with RA, the area under the curve was 0.783±0.047 (95% CI: 0.691–0.874; p<0.001), with a cut-off point of 143 ng/ml, specificity 96%, sensitivity 36.7%.In the ACCP(+) RA group, the erosion count was statistically significantly higher (p=0.044) in anti-CarP(+) patients than in anti-CarP(–) patients. A weak direct correlation between anti-CarP and DAS28 was found in the ACCP(–) RA group.Conclusion. We studied the predictive value of anti-CarP as an adjuvant biomarker in ACCP(+) and ACCP(–) subtypes of RA. ACCP(+), anti-CarP(+) patients have a more “erosive” subtype of the disease than ACCP(+), anti-CarP(–) patients. In ACCP(+) patients, anti-CarP helps to identify a more erosive subtype of the disease, and among ACCP(–) patients, it helps to reduce the proportion of seronegative patients. Further studies are needed to determine the optimal standards for the laboratory diagnosis of anti-CarP and to clarify the diagnostic potential of these antibodies as part of the differential diagnosis of arthritis in other rheumatic diseases.