title: Anti-type II collagen antibodies, anti-CCP, IgA RF and IgM RF are associated with joint damage, assessed eight years after onset of juvenile idiopathic arthritis (JIA).
abstract: BACKGROUND
  Early appearance of antibodies specific for native human type II collagen (anti-CII) characterizes an early inflammatory and destructive phenotype in adults with rheumatoid arthritis (RA). The objective of this study was to investigate the occurrence of anti-CII, IgM RF, IgA RF and anti-CCP in serum samples obtained early after diagnosis, and to relate the occurrence of autoantibodies to outcome after eight years of disease in children with juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  The Nordic JIA database prospectively included JIA patients followed for eight years with data on remission and joint damage. From this database, serum samples collected from 192 patients, at a median of four months after disease onset, were analysed for IgG anti-CII, IgM RF, IgA RF and IgG anti-CCP. Joint damage was assessed based on Juvenile Arthritis Damage Index for Articular damage (JADI-A), a validated clinical instrument for joint damage.
  
  
  RESULTS
  Elevated serum levels of anti-CII occurred in 3.1%, IgM RF in 3.6%, IgA RF in 3.1% and anti-CCP in 2.6% of the patients. Occurrence of RF and anti-CCP did to some extent overlap, but rarely with anti-CII. The polyarticular and oligoarticular extended categories were overrepresented in patients with two or more autoantibodies. Anti-CII occurred in younger children, usually without overlap with the other autoantibodies and was associated with high levels of C-reactive protein (CRP) early in the disease course. All four autoantibodies were significantly associated with joint damage, but not with active disease at the eight-year follow up.
  
  
  CONCLUSIONS
  Anti-CII, anti-CCP, IgA RF and IgM RF detected early in the disease course predicted joint damage when assessed after eight years of disease. The role of anti-CII in JIA should be further studied.
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Lillemor
authors.initials: L
authors.lastname: Berntson
authors.affiliation: Department of Pediatrics, University Hospital of North Norway, Tromsø, Norway ; Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway.
authors.forename: Ellen
authors.initials: E
authors.lastname: Nordal
authors.affiliation: Department of Pediatrics, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Fasth
authors.affiliation: Department of Pediatrics, Children's Hospital, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Aalto
authors.affiliation: Århus University Hospital, Skejby, Århus, Denmark.
authors.forename: Troels
authors.initials: T
authors.lastname: Herlin
authors.affiliation: University Clinic of Pediatrics II, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Susan
authors.initials: S
authors.lastname: Nielsen
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway ; Department of Pediatrics, St. Olavs Hospital, Trondheim, Norway.
authors.forename: Marite
authors.initials: M
authors.lastname: Rygg
authors.affiliation: University Clinic of Pediatrics II, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Marek
authors.initials: M
authors.lastname: Zak
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Rönnelid
mesh_terms: D000328:Adult; D017668:Age of Onset; D001171:Arthritis, Juvenile / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002648:Child; D024043:Collagen Type II / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D011379:Prognosis; D012217:Rheumatoid Factor / Q000097:blood; D012537:Scandinavian and Nordic Countries / Q000453:epidemiology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D024043:Collagen Type II; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D012217:Rheumatoid Factor
keywords: Anti-CCP; Anti-collagen type II antibodies; Arthritis; Child; Joints; Juvenile Idiopathic Arthritis; Rheumatoid factor