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. 2013 Mar;14(2):97-105.
doi: 10.1111/j.1399-5448.2012.00916.x. Epub 2012 Sep 10.

Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes

C Andersson  1 , F Vaziri-Sani, Aj Delli, B Lindblad, A Carlsson, G Forsander, J Ludvigsson, C Marcus, U Samuelsson, Sa Ivarsson, A Lernmark, H Elding Larsson; BDD Study Group
Collaborators, Affiliations

Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes

C Andersson et al. Pediatr Diabetes. 2013 Mar.

Abstract

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.

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