Members of the BDD Study group are listed in the Appendix.
Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes
Article first published online: 10 SEP 2012
© 2012 John Wiley & Sons A/S
Volume 14, Issue 2, pages 97–105, March 2013
How to Cite
the BDD Study group. Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes., , , , , , , , , , , ,
- Issue published online: 25 FEB 2013
- Article first published online: 10 SEP 2012
- Manuscript Accepted: 6 JUL 2012
- Manuscript Revised: 8 JUN 2012
- Manuscript Received: 14 FEB 2012
- Swedish Research Council. Grant Number: 14064
- Swedish Child Diabetes Foundation
- Swedish Diabetes Association
- National Institutes of Health. Grant Number: DK26190
- UMAS Fund
- Knut and Alice Wallenberg Foundation
- Skåne County Council for Research and Development
- diabetes mellitus;
- GAD65 autoantibodies;
- HLA genotype;
- IA-2 autoantibodies;
- insulin autoantibodies;
- type 1 diabetes;
- Zinc transporter;
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).
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).
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).
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.