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Åke Lernmark

Principal investigator

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The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes.

Author

  • Cecilia K Andersson
  • Karin Larsson
  • Fariba Vaziri Sani
  • Kristian Lynch
  • Annelie Carlsson
  • E Cedervall
  • B Jönsson
  • J Neiderud
  • Majvi Månsson
  • Anna-Lena Nilsson
  • Åke Lernmark
  • Helena Larsson
  • Sten Ivarsson

Summary, in English

Aims: We tested whether autoantibodies to all three ZnT8RWQ variants, GAD65, insulinoma-associated protein 2 (IA-2), insulin and autoantibodies to islet cell cytoplasm (ICA) in combination with human leukocyte antigen (HLA) would improve the diagnostic sensitivity of childhood type 1 diabetes by detecting the children who otherwise would have been autoantibody-negative. Methods: A total of 686 patients diagnosed in 1996-2005 in Skåne were analyzed for all the seven autoantibodies [arginin 325 zinc transporter 8 autoantibody (ZnT8RA), tryptophan 325 zinc transporter 8 autoantibody (ZnT8WA), glutamine 325 Zinc transporter 8 autoantibody (ZnT8QA), autoantibodies to glutamic acid decarboxylase (GADA), Autoantibodies to islet-antigen-2 (IA-2A), insulin autoantibodies (IAA) and ICA] in addition to HLA-DQ genotypes. Results: Zinc transporter 8 autoantibody to either one or all three amino acid variants at position 325 (ZnT8RWQA) was found in 65% (449/686) of the patients. The frequency was independent of age at diagnosis. The ZnT8RWQA reduced the frequency of autoantibody-negative patients from 7.5 to 5.4%-a reduction by 28%. Only 2 of 108 (2%) patients who are below 5 years of age had no autoantibody at diagnosis. Diagnosis without any islet autoantibody increased with increasing age at onset. DQA1-B1(*)X-0604 was associated with both ZnT8RA (p = 0.002) and ZnT8WA (p = 0.01) but not with ZnT8QA (p = 0.07). Kappa agreement analysis showed moderate (>0.40) to fair (>0.20) agreement between pairs of autoantibodies for all combinations of GADA, IA-2A, ZnT8RWQA and ICA but only slight ( < 0.19) agreement for any combination with IAA. Conclusions: This study revealed that (1) the ZnT8RWQA was common, independent of age; (2) multiple autoantibodies were common among the young; (3) DQA1-B1(*)X-0604 increased the risk for ZnT8RA and ZnT8WA; (4) agreement between autoantibody pairs was common for all combinations except IAA. These results suggest that ZnT8RWQA is a necessary complement to the classification and prediction of childhood type 1 diabetes as well as to randomize the subjects in the prevention and intervention of clinical trials.

Department/s

  • Paediatric Endocrinology
  • Paediatrics (Lund)
  • Diabetes and Celiac Unit
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2011

Language

English

Pages

394-405

Publication/Series

Autoimmunity

Volume

44

Document type

Journal article

Publisher

Taylor & Francis

Topic

  • Rheumatology and Autoimmunity

Status

Published

Research group

  • Paediatric Endocrinology
  • Diabetes and Celiac Unit

ISBN/ISSN/Other

  • ISSN: 0891-6934