title: Separate and overlapping specificities in rheumatoid arthritis antibodies binding to citrulline- and homocitrulline-containing peptides related to type I and II collagen telopeptides.
abstract: BACKGROUND
  Our objective was to find out if there are antibodies binding to homocitrulline-containing type I and II collagen carboxyterminal telopeptides in sera of patients with rheumatoid arthritis (RA), and if these antibodies cross-react with citrulline and homocitrulline in the same peptide sequence.
  
  
  METHODS
  A total of 72 RA and 72 control sera were analyzed for binding using enzyme-linked immunosorbent assay to citrulline- or homocitrulline-containing type I and II collagen carboxyterminal telopeptides, as well as to cyclic citrullinated peptide (CCP) and to mutated citrullinated vimentin (MCV). Specificities of the antibodies were tested using inhibition-ELISA.
  
  
  RESULTS
  Of the RA sera, 39 (54%) and 41 (57%) were positive for binding to CCP and MCV, respectively. Further, 34 (47%) and 30 (42%) of the patients had specific antibodies binding to and being inhibited by citrulline-containing type I collagen telopeptides and by citrulline-containing type II collagen carboxyterminal telopeptides, respectively. The corresponding figures regarding homocitrulline-containing type I and homocitrulline-containing type II collagen telopeptides were 16 (22%) and 14 (19%). Most of the patients, who were seropositive for citrullinated peptides, showed binding in multiple assays. A total of 10 (14%) RA patients were positive for all the tested peptide pairs, while 28 (39%) of them had antibodies that contained overlapping specifities between citrulline and homocitrulline in the same peptide sequence.
  
  
  CONCLUSIONS
  Antibodies to both citrulline and homocitrulline containing type I and II collagen telopeptides can be found in sera of RA patients. These antibodies are not constant from one RA patient to another, but contain separate or overlapping specificities within the same peptide sequence varying between individuals. Our results suggest some relationship between citrulline and homocitrulline-recognizing antibodies, since homocitrulline antibodies exist mainly in individuals seropositive to anti-CCP and anti-MCV.
authors.affiliation: Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland. sanna.turunen@oulu.fi.|Northern Laboratory Centre NordLab and Medical Research Centre, Oulu University Hospital, Oulu, Finland. sanna.turunen@oulu.fi.
authors.forename: Sanna
authors.initials: S
authors.lastname: Turunen
authors.affiliation: Department of Medicine, Central Hospital, Jyväskylä, Finland. pekka.hannonen@ksshp.fi.
authors.forename: Pekka
authors.initials: P
authors.lastname: Hannonen
authors.affiliation: Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland. marja-kaisa.koivula@oulu.fi.|Northern Laboratory Centre NordLab and Medical Research Centre, Oulu University Hospital, Oulu, Finland. marja-kaisa.koivula@oulu.fi.
authors.forename: Marja-Kaisa
authors.initials: MK
authors.lastname: Koivula
authors.affiliation: Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland. leila.risteli@oulu.fi.|Northern Laboratory Centre NordLab and Medical Research Centre, Oulu University Hospital, Oulu, Finland. leila.risteli@oulu.fi.
authors.forename: Leila
authors.initials: L
authors.lastname: Risteli
authors.affiliation: Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu, P.O. Box 5000, Oulu, FI-90014, Finland. juha.risteli@oulu.fi.|Northern Laboratory Centre NordLab and Medical Research Centre, Oulu University Hospital, Oulu, Finland. juha.risteli@oulu.fi.
authors.forename: Juha
authors.initials: J
authors.lastname: Risteli
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis; D001323:Autoantibodies / Q000097:blood*; D002956:Citrulline / Q000031:analogs & derivatives* / Q000097:blood*; D015331:Cohort Studies; D024042:Collagen Type I / Q000097:blood*; D024043:Collagen Type II / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000097:blood; D011485:Protein Binding / Q000502:physiology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D024042:Collagen Type I; D024043:Collagen Type II; D010455:Peptides; C001352:homocitrulline; D002956:Citrulline