title: Extended family history of autoimmune diseases and phenotype and genotype of children with newly diagnosed type 1 diabetes.
abstract: OBJECTIVE
  Based on the concept of clustering autoimmunity, children with a positive family history of autoimmunity could be expected to have a different pathogenetic form of type 1 diabetes (T1D) and thus a stronger autoimmune reactivity against β-cells and an increased prevalence of the HLA-DR3-DQ2 haplotype.
  
  
  METHODS
  We tested this hypothesis in a cross-sectional observational study from the Finnish Pediatric Diabetes Register. HLA class II genotypes and β-cell autoantibodies were analyzed, and data on the extended family history of autoimmunity and clinical markers at diagnosis were collected with a structured questionnaire from 1488 children diagnosed with T1D under the age of 15 years (57% males).
  
  
  RESULTS
  Only 23 children (1.5%) had another autoimmune disease (AID) known at diagnosis, and they had a milder metabolic decompensation at diabetes presentation. One-third (31.4%) had at least one relative with an AID other than T1D with affected mothers being overrepresented (8.2%) compared with fathers (2.8%). The children with a positive family history of other AIDs had higher levels of islet cell antibodies (P=0.003), and the HLA-DR3-DQ2 haplotype in the children was associated with celiac disease in the extended family (P<0.001), but not with an increased frequency of autoimmune disorders, in general.
  
  
  CONCLUSIONS
  Approximately one-third of children with newly diagnosed T1D have a first- and/or second-degree relative affected by an AID. Our data do not consistently support the hypothesis of differential pathogenetic mechanisms in such children.
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Central Hospital, PO Box 22, FI-00014 Helsinki, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Parkkola
authors.forename: Taina
authors.initials: T
authors.lastname: Härkönen
authors.forename: Samppa J
authors.initials: SJ
authors.lastname: Ryhänen
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D005190:Family; D005260:Female; D005387:Finland / Q000453:epidemiology; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D015803:HLA-DR3 Antigen / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes / Q000235:genetics / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D012042:Registries; D012044:Regression Analysis
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D015803:HLA-DR3 Antigen