title: Selected cyclic citrullinated peptides derived from the sequence of mutated and citrullinated vimentin (MCV) are targeted by different antibodies subclasses in patients with rheumatoid arthritis in Russian patients.
abstract: OBJECTIVE
  Antibodies against citrullinated antigens (ACPA) represent one rheumatoid arthritis (RA) classification criteria. Recently, mutated and citrullinated vimentin (MCV), containing approx. 45 potentially citrullinated sites, was characterised as another modified autoantigenic RA target. Therefore, we wanted to screen, select and validate predominant MCV autoantigenic epitopes (called here MCE) as possible new diagnostic targets.
  
  
  METHODS
  MCV-derived peptides with citrullinated sites were screened in healthy controls and patients. Based on this, twelve selected MCE were used for validation of ACPA isotypes (IgA/IgG/IgM) with ELISA in early RA (ERA, <12 months) and established RA (>12 months) Russian patients. Sensitivity of MCE reactivity was compared to commercially available ELISAs for anti-CCP IgG, anti-MCV IgG, and anti-RF IgA/IgM/IgG.
  
  
  RESULTS
  Anti-MCE IgG/IgA//IgM antibodies were observed in 64.1%, 23.1%, and 15.4% ERA, and 63.9%, 26.7%, and 13.1% established RA patients, respectively. Anti-MCV IgG was present in 64.1% ERA and 55.0% RA patients. Furthermore, anti-CCP IgG and RF IgG/IgA/IgM were detectable in up to 76.9%, 71.8%, 71.8%, and 38.5% ERA, and 80.1%, 72.3%, 67.5%, and 43.0% RA patients. Anti-CCP IgG single positivity was observed in 7.7% ERA and 6.3% RA patients. Only one RA patient was anti-MCE single positive.
  
  
  CONCLUSIONS
  MCV autoantigenic epitopes were emulated by cyclic citrullinated MCV-derived peptides and recognised by all autoantibody-Ig subclasses in RA. Tested MCE were recognized more frequently by IgG as the original MCV antigen. High antibody prevalence against CCP epitopes suggests a strong CCP-linkage to RA pathogenesis in the investigated Russian cohort.
authors.affiliation: Clinic for Rheumatology and Clinical Immunology, Charite University Hospital, Berlin, Germany. o.dergan@gmail.com.
authors.forename: Olga
authors.initials: O
authors.lastname: Derganova
authors.forename: Lorena
authors.initials: L
authors.lastname: Martinez-Gamboa
authors.forename: Karl
authors.initials: K
authors.lastname: Egerer
authors.forename: Holger
authors.initials: H
authors.lastname: Bang
authors.forename: Gert
authors.initials: G
authors.lastname: Fredenhagen
authors.forename: Dirk
authors.initials: D
authors.lastname: Roggenbuck
authors.forename: Igor
authors.initials: I
authors.lastname: Esaulenko
authors.forename: Gerd Rüdiger
authors.initials: GR
authors.lastname: Burmester
authors.forename: Tatiana
authors.initials: T
authors.lastname: Chernykh
authors.forename: Eugen
authors.initials: E
authors.lastname: Feist
mesh_terms: D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000145:classification; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000235:genetics / Q000276:immunology*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012426:Russia; D014746:Vimentin / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D000939:Epitopes; D010456:Peptides, Cyclic; D014746:Vimentin; C487763:cyclic citrullinated peptide