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Carina Törn

Coordinator

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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

Summary, in 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.

Department/s

  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Cardiology
  • Diabetes and Celiac Unit
  • Paediatrics (Lund)
  • PediatricCeliaki/Diabetes
  • Paediatric Endocrinology

Publishing year

2017-03

Language

English

Pages

735-740

Publication/Series

Diabetes

Volume

66

Issue

3

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Keywords

  • Journal Article

Status

Published

Research group

  • Diabetes and Celiac Unit
  • PediatricCeliaki/Diabetes
  • Paediatric Endocrinology

ISBN/ISSN/Other

  • ISSN: 1939-327X