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Doubly reactive INS-IGF2 autoantibodies in children with newly diagnosed autoimmune (type 1) diabetes.

Kanatsuna, Norio LU ; Delli, Ahmed LU ; Andersson, Cecilia K LU ; Nilsson, Anna-Lena LU ; Vaziri Sani, Fariba LU ; Larsson, Karin LU ; Carlsson, Annelie LU ; Cedervall, Elisabeth; Jönsson, Björn and Neiderud, Jan LU , et al. (2015) In Scandinavian Journal of Immunology 82(4). p.361-369
Abstract
The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ, or both, in newly diagnosed type 1 diabetes patients and controls. Patients (n=676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n=363) were analyzed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, and ZnT8QA, and HLA-DQ genotypes were also... (More)
The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ, or both, in newly diagnosed type 1 diabetes patients and controls. Patients (n=676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n=363) were analyzed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, and ZnT8QA, and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than controls (p<0.001). Irrespective of age at diagnosis, 19 % (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (p<0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR=1.509; 95th CI 1.011, 2.252; p=0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans, rather than cis heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes. This article is protected by copyright. All rights reserved. (Less)
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published
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Scandinavian Journal of Immunology
volume
82
issue
4
pages
361 - 369
publisher
Wiley-Blackwell
external identifiers
  • pmid:26073034
  • wos:000361142600008
  • scopus:84941067367
ISSN
1365-3083
DOI
10.1111/sji.12325
language
English
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yes
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df88e2df-1c44-4bca-a95f-92c558591019 (old id 7486352)
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http://www.ncbi.nlm.nih.gov/pubmed/26073034?dopt=Abstract
date added to LUP
2015-07-08 15:22:58
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2017-01-01 03:50:57
@article{df88e2df-1c44-4bca-a95f-92c558591019,
  abstract     = {The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ, or both, in newly diagnosed type 1 diabetes patients and controls. Patients (n=676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n=363) were analyzed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, and ZnT8QA, and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than controls (p&lt;0.001). Irrespective of age at diagnosis, 19 % (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (p&lt;0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR=1.509; 95th CI 1.011, 2.252; p=0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans, rather than cis heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes. This article is protected by copyright. All rights reserved.},
  author       = {Kanatsuna, Norio and Delli, Ahmed and Andersson, Cecilia K and Nilsson, Anna-Lena and Vaziri Sani, Fariba and Larsson, Karin and Carlsson, Annelie and Cedervall, Elisabeth and Jönsson, Björn and Neiderud, Jan and Larsson, Helena and Ivarsson, Sten and Törn, Carina and Fex, Malin and Lernmark, Åke},
  issn         = {1365-3083},
  language     = {eng},
  number       = {4},
  pages        = {361--369},
  publisher    = {Wiley-Blackwell},
  series       = {Scandinavian Journal of Immunology},
  title        = {Doubly reactive INS-IGF2 autoantibodies in children with newly diagnosed autoimmune (type 1) diabetes.},
  url          = {http://dx.doi.org/10.1111/sji.12325},
  volume       = {82},
  year         = {2015},
}