Background The determination of antibodies (abs) against citrullinated antigens (ACPA) nowadays belongs to the diagnostic tests included in the classification criteria for rheumatoid arthritis (RA). However, the standard cyclic citrullinated peptide antigen (CCP) is artificial and not expressed in the targeted tissues. Recently, mutated and citrullinated vimentin (MCV) was isolated and characterized as another modified autoantigen in RA. It is of interest, whether cyclic peptides from the sequence of MCV are also recognized as antigenic epitopes.
Objectives To analyse reactivity against cyclic citrullinated peptides derived from the sequence of MCV in a cohort of patients with early (ERA) and established (RA).
Methods Immunglobulin subclass (IgA, IgG and IgM) ab against MCV-cyclic epitopes (MCE, Orgentec) were investigated in a cohort of well characterized Russian patients (n=206) with RA using ELISA. Sensitivity of MCE-reactivity was compared to commercially available ELISAs for anti-CCP IgG (Medipan), anti-RF (IgA, IgG and IgG), and anti-MCV IgG ab (Orgentec). Patients were classified according to the duration of disease as ERA (<12 months; n=34) or established RA (>12 months; n=172).
Results Abs isotypes IgG, IgA and IgM against MCE were observed in 64.7%, 23% and 17.6% of patients with ERA, as well as in 68.6%, 27.3% and 13.7% of patients with RA, respectively. Anti-MCV ab IgG were found positive in 61.8% of patients with ERA, and in 55.8% of patients with RA. Thus, the frequency of IgG-ab against MCE was even higher compared to the complete MCV antigen. In comparison, anti-CCP IgG ab and RF IgG, IgA and IgM were detectable in 73.5%, 70.6, 64.7%, and 35.3% of patients with ERA, and in 80.2%, 71.5%, 68.6%, and 41.9% of patients with RA, respectively. Single positive results for CCP IgG ab were observed in 8.8% of ERA and 10.5% of RA patients. By summarizing all MCE subclass abs, single positive results were observed in 11.8% of ERA and 2.3% of RA patients. The highest IgG ACPA titers were measured for the anti-CCP (mean ERA 2274.9 U/ml and RA 1890.1 U/ml) and the anti-MCE IgG ab (mean ERA 516.0 U/ml and RA 591.6 U/ml) followed by anti-MCV ab (mean ERA 338.0 U/ml and RA 443.7 U/ml).
Conclusions The antigenic epitopes of MCV are maintained by using cyclic citrullinated peptides. Antibody reactivity against MCE includes all subclasses, with a predominance of IgG-ab. For diagnostic purposes, the standard CCP ELISA provided the highest sensitivity in the analysed cohort.
Disclosure of Interest O. Derganowa: None Declared, L. Martinez-Gamboa: None Declared, K. Egerer: None Declared, H. Bang Employee of: Orgentec, D. Roggenbuck Employee of: Medipan, I. Esaulenko: None Declared, G. Burmester: None Declared, T. Chernykh: None Declared, E. Feist: None Declared