Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes.
2013 (English)In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 14, no 2, 97-105 p.Article in journal (Refereed) Published
OBJECTIVE: To establish the diagnostic sensitivity of and the relationships between autoantibodies to all three Zinc transporter 8 (Zinc transporter 8 autoantibody to either one, two, or all three amino acid variants at position 325, ZnT8A) variants to human leukocyte antigen (HLA)-DQ and to autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A), and insulin (IAA).
METHODS: We analyzed 3165 patients with type 1 diabetes (T1D) in the Better Diabetes Diagnosis study for HLA-DQ genotypes and all six autoantibodies (ZnT8RA, arginine 325 Zinc transporter 8 autoantibody; ZnT8WA, tryptophan 325 Zinc transporter 8 autoantibody; ZnT8QA, glutamine 325 Zinc transporter 8 autoantibody; GADA, IA-2A, and IAA).
RESULTS: ZnT8A was found in 65% of the patients and as many as 108 of 3165 (3.4%) had 1-3 ZnT8A alone. None had ZnT8QA alone. Together with GADA (56%), IA-2A (73%), and IAA (33%), 93% of the T1D patients were autoantibody positive. All three ZnT8A were less frequent in children below 2 yr of age (p < 0.0001). All three ZnT8A were associated with DQA1-B1*X-0604 (DQ6.4) and DQA1-B1*03-0302 (DQ8). ZnT8WA and ZnT8QA were negatively associated with DQA1-B1*05-02 (DQ2).
CONCLUSIONS: Analysis of ZnT8A increased the diagnostic sensitivity of islet autoantibodies for T1D as only 7% remained islet autoantibody negative. The association between DQ6.4 and all three ZnT8A may be related to ZnT8 antigen presentation by the DQ6.4 heterodimer.
Place, publisher, year, edition, pages
2013. Vol. 14, no 2, 97-105 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-222288DOI: 10.1111/j.1399-5448.2012.00916.xPubMedID: 22957668OAI: oai:DiVA.org:uu-222288DiVA: diva2:711194
Co-author: Ingemar Swenne, Uppsala universitet, institutionen för kvinnors och barns hälsa, forskargrupp Barnendokrinologisk forskning, ingår i members of the BDD Study group.2014-04-092014-04-092016-10-03Bibliographically approved