title: Juvenile arthritis and autoimmunity to type II collagen.
abstract: OBJECTIVE
  Joint inflammation in juvenile rheumatoid arthritis (JRA) is sometimes associated with an autoimmune response to type II collagen (CII), a cartilage-specific protein. To test the hypothesis that down-regulation of autoimmunity to CII can be accomplished in JRA by oral administration of CII, an open-label study of CII was performed in 9 patients with JRA.
  
  
  METHODS
  Seven rheumatoid factor-negative JRA patients with polyarticular disease and 2 JRA patients with pauciarticular disease (1 with early onset and 1 with late onset) were treated for 3 months with oral bovine CII. Patients were examined for disease activity and underwent routine laboratory testing at monthly intervals. Two of the patients had flares of disease when treatment was discontinued, and these patients were re-treated for an additional 3 months. To test the hypothesis that oral tolerance induces an immune deviation of T cells, peripheral blood mononuclear cells from patients were collected before and after treatment and cultured with CII. Supernatants and RNA were collected and analyzed for the presence of various cytokines.
  
  
  RESULTS
  Eight patient trials met the criteria for clinical improvement outlined by Giannini and coworkers in 1997. None of the patients had any side effects from the treatment. In 6 of the 8 patients who improved, interferon-gamma production decreased after oral CII therapy, correlating with clinical improvement, while 6 patients had increases in levels of transforming growth factor beta3.
  
  
  CONCLUSIONS
  These results are encouraging. The possible beneficial effect of oral CII in JRA merits further investigation.
authors.affiliation: University of Tennessee, Memphis, USA.
authors.forename: L K
authors.initials: LK
authors.lastname: Myers
authors.forename: G C
authors.initials: GC
authors.lastname: Higgins
authors.forename: T H
authors.initials: TH
authors.lastname: Finkel
authors.forename: A M
authors.initials: AM
authors.lastname: Reed
authors.forename: J W
authors.initials: JW
authors.lastname: Thompson
authors.forename: R C
authors.initials: RC
authors.lastname: Walton
authors.forename: J
authors.initials: J
authors.lastname: Hendrickson
authors.forename: N C
authors.initials: NC
authors.lastname: Kerr
authors.forename: R K
authors.initials: RK
authors.lastname: Pandya-Lipman
authors.forename: B V
authors.initials: BV
authors.lastname: Shlopov
authors.forename: P
authors.initials: P
authors.lastname: Stastny
authors.forename: A E
authors.initials: AE
authors.lastname: Postlethwaite
authors.forename: A H
authors.initials: AH
authors.lastname: Kang
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D001171:Arthritis, Juvenile / Q000276:immunology* / Q000628:therapy*; D001324:Autoantigens / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015551:Autoimmunity; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D001324:Autoantigens; D016207:Cytokines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D003094:Collagen