title: [An evaluation of HLA class 2 alleles and anti-islet antibodies as evidence for non-autoimmune diabetes in Wolfram syndrome].
abstract: BACKGROUND
  A clinical criterion of the Wolfram syndrome is the coexistence of diabetes and optic atrophy recognized before the age of 15. Diabetes present in Wolfram syndrome is a result of the selective β cell loss and failed insulin secretion which is probably associated with non-autoimmune pathogenesis.
  
  
  OBJECTIVE
  The aim of the study was an evaluation of HLA subtypes and presence of β-cell autoantibodies in patients with molecularly confirmed Wolfram syndrome.
  
  
  METHODS
  9 patients with Wolfram syndrome aged 10-24 years were examined. We also studied 218 patients with type 1 diabetes as a reference group. A control group of 176 healthy individuals was included in the study. Besides the clinical assessment the HLA typing by PCR-SSO was performed. Islet cell antibodies (ICA), antibodies to glutamic acid decarboxylase (GADA), thyrosine phosphatase antibodies (IA2A) and insulin antibodies (IAA) were also detected.
  
  
  RESULTS
  In all nine patients the coexistence of diabetes with optic atrophy was observed and in 8/9 individuals additional symptoms were recognized. In patients with Wolfram syndrome a significantly lower age of diagnosis of diabetes (Me=5.0 years) than in type 1 diabetic children (Me=10.4; p=0.002) was observed. Studies of HLA subtypes demonstrated an increased prevalence of HLA-DQw1, DRB1⋅03 and/or 04 and DR2. A comparison of the frequency of the HLA alleles in patients with Wolfram syndrome with type 1 diabetic children showed a more frequent presence of the DRB1⋅1501 (p=0.03; OR=13.28 (2.44-72.12)) and DQB1⋅06 (p=0.016; OR=10.15 (2.49-41.35)) alleles in patients with Wolfram syndrome.
  
  
  CONCLUSIONS
  Polish patients with Wolfram syndrome have a different profile of the HLA antigens with the presence of DR2, DQw1 and DRB3/4 allele and are negative for diabetes-related autoantibodies, which may confirm non-autoimmune β-cell destruction in this syndrome.
authors: Klinika Pediatrii, Katedry Pediatrii Uniwersytetu Medycznego w Lodzi. agnieszka.zmyslowska@umed.lodz.pl
authors: Agnieszka
authors: A
authors: Zmysłowska
authors: Maciej
authors: M
authors: Borowiec
authors: Karolina
authors: K
authors: Antosik
authors: Krystyna
authors: K
authors: Wyka
authors: Agnieszka
authors: A
authors: Cieślik-Heinrich
authors: Izabela
authors: I
authors: Klich
authors: Wojciech
authors: W
authors: Młynarski
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000235:genetics* / Q000276:immunology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D015802:HLA-DR2 Antigen / Q000235:genetics / Q000276:immunology; D059826:HLA-DRB3 Chains; D059845:HLA-DRB4 Chains; D006801:Humans; D008297:Male; D014929:Wolfram Syndrome / Q000235:genetics* / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D015802:HLA-DR2 Antigen; D059826:HLA-DRB3 Chains; D059845:HLA-DRB4 Chains; C024211:islet cell antibody