title: HLA class II haplotype and autoantibody associations in children with juvenile dermatomyositis and juvenile dermatomyositis-scleroderma overlap.
abstract: OBJECTIVE
  To investigate a large cohort of children with juvenile dermatomyositis (JDM), and those with JDM-scleroderma (JDM-SSc) overlap, using detailed serological analysis, HLA class II genotyping and clinical characterization.
  
  
  METHODS
  Children (114) with JDM were recruited, and clinical data collected, through the JDM National Registry and Repository (UK and Ireland). Sera were assayed for ANA using standard immunofluorescence techniques and specific antibodies characterized using ELISA, immunodiffusion and radioimmunoprecipitation. Patients and controls (n = 537) were genotyped at the HLA-DRB1 and DQB1 loci, and then the DQA1 locus data was derived.
  
  
  RESULTS
  Over 70% of the patients were ANA-positive. Clear differences in serological and genetic data were demonstrated between JDM and JDM-SSc overlap groups. Strong associations were seen for HLA-DRB1*03 (all cases vs controls, P(corr) = 0.02; JDM-SSc vs controls, P(corr) = 0.001) and HLA-DQA1*05 (all cases vs controls, P(corr) = 0.01; JDM-SSc vs controls, P(corr) = 0.005). The frequency of the HLA-DRB1*03-DQA1*05-DQB1*02 haplotype was significantly increased in the JDM-SSc (P = 0.003) and anti-PM-Scl antibody (P = 0.002) positive groups. All anti-U1-RNP antibody-positive patients had at least one copy of HLA-DRB1*04-DQA1*03-DQB1*03 haplotype. Associations were observed between serology and specific clinical features.
  
  
  CONCLUSIONS
  We present clinical data, HLA genotyping and serological profiling on a large cohort of JDM patients and a carefully characterized subset of patients with JDM-SSc overlap. The results confirm known HLA associations and extend the knowledge by stratification of data in serological and clinical subgroups. In the future, a combination of serological and genetic typing may allow for better prediction of clinical course and disease subtype in JDM.
authors.affiliation: Rheumatology Unit, Institute of Child Health, UCL, 30 Guilford Street, London WC1N 1EH, UK. l.wedderburn@ich.ucl.ac.uk
authors.forename: L R
authors.initials: LR
authors.lastname: Wedderburn
authors.forename: N J
authors.initials: NJ
authors.lastname: McHugh
authors.forename: H
authors.initials: H
authors.lastname: Chinoy
authors.forename: R G
authors.initials: RG
authors.lastname: Cooper
authors.forename: F
authors.initials: F
authors.lastname: Salway
authors.forename: W E R
authors.initials: WE
authors.lastname: Ollier
authors.forename: L J
authors.initials: LJ
authors.lastname: McCann
authors.forename: H
authors.initials: H
authors.lastname: Varsani
authors.forename: J
authors.initials: J
authors.lastname: Dunphy
authors.forename: J
authors.initials: J
authors.lastname: North
authors.forename: J E
authors.initials: JE
authors.lastname: Davidson
mesh_terms: D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003882:Dermatomyositis / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II