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Glutamate decarboxylase-, insulin-, and islet cell-antibodies and HLA typing to detect diabetes in a general population-based study of Swedish children

Hagopian, William A. ; Sanjeevi, Carani B. ; Kockum, Ingrid ; Landin-Olsson, Mona LU ; Karlsen, Allan E. LU ; Sundkvist, Göran LU ; Dahlquist, Gisela ; Palmer, Jerry and Lernmark, Åke LU orcid (1995) In Journal of Clinical Investigation 95(4). p.1505-1511
Abstract

Most autoimmune diabetes occurs in those without a diabetic relative, but few cases are identifiable prospectively. To model general population prediction, 491 consecutive newly diabetic children from all of Sweden were tested for autoantibodies to glutamate decarboxylase (GAD65ab), insulin (IAA), and islet cells (ICA), and for HLA-DQ genotypes by PCR; 415 matched control children were tested in parallel. GAD65ab sensitivity/specificity was 70/96%, versus 84/96% for ICA, 56/97% for IAA, 93/93% (any positive), 39/99.7% (all positive), and 41/99.7% (GAD65ab plus IAA). The latter's 25% predictive value was not improved by requiring concomitant high-risk HLA genotypes. GAD65ab were associated with DQA1*0501/B1*0201 (DQ2; P = 0.007) but not... (More)

Most autoimmune diabetes occurs in those without a diabetic relative, but few cases are identifiable prospectively. To model general population prediction, 491 consecutive newly diabetic children from all of Sweden were tested for autoantibodies to glutamate decarboxylase (GAD65ab), insulin (IAA), and islet cells (ICA), and for HLA-DQ genotypes by PCR; 415 matched control children were tested in parallel. GAD65ab sensitivity/specificity was 70/96%, versus 84/96% for ICA, 56/97% for IAA, 93/93% (any positive), 39/99.7% (all positive), and 41/99.7% (GAD65ab plus IAA). The latter's 25% predictive value was not improved by requiring concomitant high-risk HLA genotypes. GAD65ab were associated with DQA1*0501/B1*0201 (DQ2; P = 0.007) but not DQA1*0301/B1*0302 (DQ8), and IAA with DQA1*0301/B1*0302 (DQ8; P = 0.03) but not DQA1*0501/B1*0201 (DQ2). GAD65ab were more prevalent in females than males (79 vs. 63%; P < 0.0001) but did not vary with onset age nor season. Combining the three antibody assays yielded sufficient sensitivity for screening. GADab were relatively sensitive/specific for diabetes, but even with HLA marker combinations yielded predictive values insufficient for early immunointervention in the low-prevalence general population.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
autoimmunity, GAD, IAA, insulin-dependent diabetes, prediction
in
Journal of Clinical Investigation
volume
95
issue
4
pages
1505 - 1511
publisher
The American Society for Clinical Investigation
external identifiers
  • pmid:7706455
  • scopus:0028926815
ISSN
0021-9738
DOI
10.1172/JCI117822
language
English
LU publication?
yes
id
b0033ba3-2a14-49de-97aa-e28c65ae3bec
date added to LUP
2019-09-11 08:57:00
date last changed
2024-09-19 08:58:01
@article{b0033ba3-2a14-49de-97aa-e28c65ae3bec,
  abstract     = {{<p>Most autoimmune diabetes occurs in those without a diabetic relative, but few cases are identifiable prospectively. To model general population prediction, 491 consecutive newly diabetic children from all of Sweden were tested for autoantibodies to glutamate decarboxylase (GAD65ab), insulin (IAA), and islet cells (ICA), and for HLA-DQ genotypes by PCR; 415 matched control children were tested in parallel. GAD65ab sensitivity/specificity was 70/96%, versus 84/96% for ICA, 56/97% for IAA, 93/93% (any positive), 39/99.7% (all positive), and 41/99.7% (GAD65ab plus IAA). The latter's 25% predictive value was not improved by requiring concomitant high-risk HLA genotypes. GAD65ab were associated with DQA1*0501/B1*0201 (DQ2; P = 0.007) but not DQA1*0301/B1*0302 (DQ8), and IAA with DQA1*0301/B1*0302 (DQ8; P = 0.03) but not DQA1*0501/B1*0201 (DQ2). GAD65ab were more prevalent in females than males (79 vs. 63%; P &lt; 0.0001) but did not vary with onset age nor season. Combining the three antibody assays yielded sufficient sensitivity for screening. GADab were relatively sensitive/specific for diabetes, but even with HLA marker combinations yielded predictive values insufficient for early immunointervention in the low-prevalence general population.</p>}},
  author       = {{Hagopian, William A. and Sanjeevi, Carani B. and Kockum, Ingrid and Landin-Olsson, Mona and Karlsen, Allan E. and Sundkvist, Göran and Dahlquist, Gisela and Palmer, Jerry and Lernmark, Åke}},
  issn         = {{0021-9738}},
  keywords     = {{autoimmunity; GAD; IAA; insulin-dependent diabetes; prediction}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{4}},
  pages        = {{1505--1511}},
  publisher    = {{The American Society for Clinical Investigation}},
  series       = {{Journal of Clinical Investigation}},
  title        = {{Glutamate decarboxylase-, insulin-, and islet cell-antibodies and HLA typing to detect diabetes in a general population-based study of Swedish children}},
  url          = {{http://dx.doi.org/10.1172/JCI117822}},
  doi          = {{10.1172/JCI117822}},
  volume       = {{95}},
  year         = {{1995}},
}