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

Andersson, C ; Vaziri Sani, Fariba LU ; Delli, Aj ; Lindblad, Bengt ; Carlsson, Annelie LU orcid ; Forsander, G ; Ludvigsson, J ; Marcus, C ; Samuelsson, U and Ivarsson, Sa , et al. (2013) In Pediatric Diabetes 14(2). p.97-105
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).... (More)
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. (Less)
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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pediatric Diabetes
volume
14
issue
2
pages
97 - 105
publisher
Wiley-Blackwell
external identifiers
  • wos:000315448600003
  • pmid:22957668
  • scopus:84874547213
  • pmid:22957668
ISSN
1399-543X
DOI
10.1111/j.1399-5448.2012.00916.x
project
Better Diabetes Diagnosis (BDD)
language
English
LU publication?
yes
id
ce7cb2a5-9771-4ed3-8ad6-d2c0fc949efb (old id 3124179)
date added to LUP
2016-04-01 10:34:39
date last changed
2024-02-20 10:35:52
@article{ce7cb2a5-9771-4ed3-8ad6-d2c0fc949efb,
  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 &lt; 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.}},
  author       = {{Andersson, C and Vaziri Sani, Fariba and Delli, Aj and Lindblad, Bengt and Carlsson, Annelie and Forsander, G and Ludvigsson, J and Marcus, C and Samuelsson, U and Ivarsson, Sa and Lernmark, Åke and Elding Larsson, H}},
  issn         = {{1399-543X}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{97--105}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Pediatric Diabetes}},
  title        = {{Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes.}},
  url          = {{http://dx.doi.org/10.1111/j.1399-5448.2012.00916.x}},
  doi          = {{10.1111/j.1399-5448.2012.00916.x}},
  volume       = {{14}},
  year         = {{2013}},
}