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Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes
Lund Univeristy.
Lunds universitet.ORCID iD: 0000-0002-9953-2829
Lund University.
The Queen Silvia Children's Hospital .
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2013 (English)In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 14, no 2, 97-105 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
Diabetes mellitus; GAD65 autoantibodies; HLA genotype; IA-2 autoantibodies; insulin autoantibodies; type 1 diabetes; Zinc transporter; ZnT8
National Category
Cell and Molecular Biology Immunology in the medical area
Identifiers
URN: urn:nbn:se:hkr:diva-12679DOI: 10.1111/j.1399-5448.2012.00916.xISI: 000315448600003PubMedID: 22957668OAI: oai:DiVA.org:hkr-12679DiVA: diva2:739638
Available from: 2014-08-21 Created: 2014-08-21 Last updated: 2017-12-05Bibliographically approved

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Vaziri-Sani, Fariba

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