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

Author:
  • Norio Kanatsuna
  • Ahmed Delli
  • Cecilia K Andersson
  • Anna-Lena Nilsson
  • Fariba Vaziri Sani
  • Karin Larsson
  • Annelie Carlsson
  • Elisabeth Cedervall
  • Björn Jönsson
  • Jan Neiderud
  • Helena Larsson
  • Sten Ivarsson
  • Carina Törn
  • Malin Fex
  • Åke Lernmark
Publishing year: 2015
Language: English
Pages: 361-369
Publication/Series: Scandinavian Journal of Immunology
Volume: 82
Issue: 4
Document type: Journal article
Publisher: Wiley-Blackwell

Abstract english

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.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Diabetes and Celiac Unit
  • Paediatric Endocrinology
  • ISSN: 1365-3083
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79

60:11:015

Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00