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An Increased Diagnostic Sensitivity of Truncated GAD65 Autoantibodies in Type 1 Diabetes May Be Related to HLA-DQ8

Author:
  • Axel Wester
  • Hanna Skärstrand
  • Alexander Lind
  • Anita Ramelius
  • Annelie Carlsson
  • Elisabeth Cedervall
  • Björn Jönsson
  • Sten A Ivarsson
  • Helena Larsson
  • Karin Larsson
  • Bengt Lindberg
  • Jan Neiderud
  • Malin Fex
  • Carina Törn
  • Åke Lernmark
Publishing year: 2017-03
Language: English
Pages: 735-740
Publication/Series: Diabetes
Volume: 66
Issue: 3
Document type: Journal article
Publisher: American Diabetes Association

Abstract english

N-terminally truncated (96-585) GAD65 (tGAD65) autoantibodies may better delineate type 1 diabetes than full-length GAD65 (fGAD65) autoantibodies. We aimed to compare the diagnostic sensitivity and specificity between fGAD65 and tGAD65 autoantibodies for type 1 diabetes in relation to HLA-DQ. Sera from children and adolescents with newly diagnosed type 1 diabetes (n = 654) and healthy control subjects (n = 605) were analyzed in radiobinding assays for fGAD65 (fGADA), tGAD65 (tGADA), and commercial (125)I-GAD65 (RSRGADA) autoantibodies. The diagnostic sensitivity and specificity in the receiver operating characteristic curve did not differ between fGADA and tGADA. At the optimal cutoff, the diagnostic sensitivity for fGADA was lower than tGADA at similar diagnostic specificities. In 619 patients, 64% were positive for RSRGADA compared with 68% for fGADA and 74% for tGADA. Using non-DQ2/non-DQ8 patients as reference, the risk of being diagnosed with fGADA and tGADA was increased in patients with DQ2/2 and DQ2/8. Notably, logistic regression analysis suggested that DQ8/8 patients had an increased risk to be diagnosed with tGADA (P = 0.003) compared with fGADA (P = 0.09). tGADA had a higher diagnostic sensitivity for type 1 diabetes than both fGADA and RSRGADA. As DQ8/8 patients represent 10-11% of patients with newly diagnosed type 1 diabetes <18 years of age, tGADA analysis should prove useful for disease classification.

Keywords

  • Endocrinology and Diabetes
  • Journal Article

Other

Published
  • Diabetes and Celiac Unit
  • PediatricCeliaki/Diabetes
  • Paediatric Endocrinology
  • ISSN: 1939-327X
E-mail: anita.ramelius [at] med.lu.se

Biomedical analyst

Diabetes and Celiac Unit

+46 40 39 19 06

91:10:018

Jan Waldenströms gata 35, Malmö

36

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00