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

Wester, Axel; Skärstrand, Hanna LU ; Lind, Alexander LU ; Ramelius, Anita LU ; Carlsson, Annelie LU ; Cedervall, Elisabeth; Jönsson, Björn; Ivarsson, Sten A LU ; Larsson, Helena LU and Larsson, Karin, et al. (2017) In Diabetes 66(3). p.735-740
Abstract

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... (More)

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.

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publication status
published
subject
keywords
Journal Article
in
Diabetes
volume
66
issue
3
pages
6 pages
publisher
American Diabetes Association Inc.
external identifiers
  • scopus:85016457125
  • wos:000394634100018
ISSN
1939-327X
DOI
10.2337/db16-0891
language
English
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yes
id
04409314-c1ca-4358-b73f-baa6e951798b
date added to LUP
2017-03-21 16:14:59
date last changed
2018-03-11 04:38:38
@article{04409314-c1ca-4358-b73f-baa6e951798b,
  abstract     = {<p>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 &lt;18 years of age, tGADA analysis should prove useful for disease classification.</p>},
  author       = {Wester, Axel and Skärstrand, Hanna and Lind, Alexander and Ramelius, Anita and Carlsson, Annelie and Cedervall, Elisabeth and Jönsson, Björn and Ivarsson, Sten A and Larsson, Helena and Larsson, Karin and Lindberg, Bengt and Neiderud, Jan and Fex, Malin and Törn, Carina and Lernmark, Åke},
  issn         = {1939-327X},
  keyword      = {Journal Article},
  language     = {eng},
  number       = {3},
  pages        = {735--740},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {An Increased Diagnostic Sensitivity of Truncated GAD65 Autoantibodies in Type 1 Diabetes May Be Related to HLA-DQ8},
  url          = {http://dx.doi.org/10.2337/db16-0891},
  volume       = {66},
  year         = {2017},
}