title: Interferon-α induction and detection of anti-ro, anti-la, anti-sm, and anti-rnp autoantibodies by autoantigen microarray analysis in juvenile dermatomyositis.
abstract: OBJECTIVE
  To evaluate serum interferon-α (IFNα) activity in the context of autoantibody profiles in patients with juvenile dermatomyositis (JDM).
  
  
  METHODS
  Sera from 36 patients with JDM were analyzed. Autoantibody profiles were determined by probing microarrays, which were fabricated with ∼80 distinct autoantigens, with serum and a Cy3-conjugated secondary antibody. Arrays were scanned and analyzed to determine antigen reactivity. Serum IFNα activity was measured using a functional reporter cell assay. Sera were assayed alone or in combination with cellular material released from necrotic U937 cells to stimulate peripheral blood mononuclear cells from healthy donors in vitro, and IFNα production in culture was measured by a dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA).
  
  
  RESULTS
  Reactivity against at least 1 of 41 autoantigens on the microarray, including Ro 52, Ro 60, La, Sm, and RNP, was observed in 75% of the serum samples from patients with JDM. IFNα activity was detected in 7 samples by reporter cell assay. The reporter cell assay showed a significant association of reactivity against Ro, La, Sm, and proliferating cell nuclear antigen with serum IFNα activity (P = 0.005). Significance Analysis of Microarrays (SAM) identified increased reactivity against Sm, RNP, Ro 52, U1-C, and Mi-2 in these sera. Sixteen samples induced IFNα production as measured by DELFIA, and there was a significant association of reactivity against Ro, La, Sm, and RNP with the induction of IFNα by serum and necrotic cell material (P = 0.034). SAM identified increased reactivity against Ro 60 in these sera.
  
  
  CONCLUSIONS
  These data support the hypothesis that nucleic acid-associated autoantibodies, including the Ro/La and Sm/RNP complexes, may stimulate the production of active IFNα in children with JDM.
authors.affiliation: Stanford University, Stanford, California.
authors.forename: Imelda
authors.initials: I
authors.lastname: Balboni
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Niewold
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Morgan
authors.forename: Cindy
authors.initials: C
authors.lastname: Limb
authors.forename: Maija-Leena
authors.initials: ML
authors.lastname: Eloranta
authors.forename: Lars
authors.initials: L
authors.lastname: Rönnblom
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Utz
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Pachman
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000032:analysis* / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D002648:Child; D003882:Dermatomyositis / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000097:blood / Q000276:immunology*; D008297:Male; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology; D055517:snRNP Core Proteins / Q000276:immunology; D000097585:SS-B Antigen; D000099207:SS-A Antigen
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D016898:Interferon-alpha; D017412:Ribonucleoprotein, U1 Small Nuclear; D012261:Ribonucleoproteins; D055517:snRNP Core Proteins; D000097585:SS-B Antigen; D000099207:SS-A Antigen