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The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes
Lund University.
Deparment of Paediatrics, Kristianstad hospital.
Lund University.ORCID iD: 0000-0002-9953-2829
Lund University.
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2011 (English)In: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 44, no 5, 394-405 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2011. Vol. 44, no 5, 394-405 p.
Keyword [en]
Diabetes mellitus, GAD65 autoantibodies, human leukocyte antigen genotype, IA-2 autoantibodies, islet cell cytoplasm, insulin autoantibodies
National Category
Immunology in the medical area Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:hkr:diva-12668DOI: 10.3109/08916934.2010.540604ISI: 000292567000006PubMedID: 21244337OAI: oai:DiVA.org:hkr-12668DiVA: diva2:739675
Available from: 2014-08-21 Created: 2014-08-21 Last updated: 2017-01-11Bibliographically approved

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CiteExportLink to record
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