title: Thyroid autoimmunity in relation to islet autoantibodies and HLA-DQ genotype in newly diagnosed type 1 diabetes in children and adolescents.
abstract: OBJECTIVE
  The aim of this work was to investigate, in children newly diagnosed with type 1 diabetes: (1) the prevalence of autoantibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb); and (2) the association between TPOAb, TGAb or both, with either islet autoantibodies or HLA-DQ genes.
  
  
  METHODS
  Blood samples from 2,433 children newly diagnosed with type 1 diabetes were analysed for TPOAb and TGAb in addition to autoantibodies against arginine zinc transporter 8 (ZnT8RA), tryptophan zinc transporter 8 (ZnT8WA), glutamine zinc transporter 8 (ZnT8QA), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), HLA-DQA-B1 genotypes, thyroid-stimulating hormone (TSH) and free thyroxine (T4).
  
  
  RESULTS
  At type 1 diabetes diagnosis, 12% of the children had thyroid autoantibodies (60% were girls; p < 0.0001). GADA was positively associated with TPOAb (p < 0.001) and with TGAb (p < 0.001). In addition, ZnT8A was associated with both TPOAb (p = 0.039) and TGAb (p = 0.015). DQB1*05:01 in any genotype was negatively associated with TPOAb (OR 0.55, 95% CI 0.37, 0.83, p value corrected for multiple comparisons (p c) = 0.012) and possibly with TGAb (OR 0.55, 95% CI 0.35, 0.87, p c = 0.07). Thyroid autoimmunity in children newly diagnosed with type 1 diabetes was rarely (0.45%) associated with onset of clinical thyroid disease based on TSH and free T4.
  
  
  CONCLUSIONS
  GADA and ZnT8A increased the risk for thyroid autoimmunity at the time of clinical diagnosis of type 1 diabetes, while HLA-DQB1*05:01 reduced the risk. However, the associations between thyroid autoimmunity and HLA-DQ genotype were weak and did not fully explain the co-occurrence of islet and thyroid autoimmunity.
authors.affiliation: Department of Clinical Sciences, Skåne University Hospital SUS, Malmö, Sweden. berglind.jonsdottir@gmail.com
authors.forename: B
authors.initials: B
authors.lastname: Jonsdottir
authors.forename: C
authors.initials: C
authors.lastname: Andersson
authors.forename: A
authors.initials: A
authors.lastname: Carlsson
authors.forename: A
authors.initials: A
authors.lastname: Delli
authors.forename: G
authors.initials: G
authors.lastname: Forsander
authors.forename: J
authors.initials: J
authors.lastname: Ludvigsson
authors.forename: C
authors.initials: C
authors.lastname: Marcus
authors.forename: U
authors.initials: U
authors.lastname: Samuelsson
authors.forename: E
authors.initials: E
authors.lastname: Ortqvist
authors.forename: A
authors.initials: A
authors.lastname: Lernmark
authors.forename: S-A
authors.initials: SA
authors.lastname: Ivarsson
authors.forename: H Elding
authors.initials: HE
authors.lastname: Larsson
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005260:Female; D005838:Genotype; D006683:HLA-DQ Antigens / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D013961:Thyroid Gland / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens