Recognition of glutamic acid decarboxylase (GAD) by autoantibodies from different GAD antibody-positive phenotypes
(2000) In Journal of Clinical Endocrinology and Metabolism 85(12). p.4671-4679- Abstract
Autoantibodies against the smaller isoform of glutamic acid decarboxylase (GAD) are markers for Type 1 diabetes. GAD65 autoantibody (GAD65Ab)-positive individuals in the general population are, however, mostly at low risk of developing Type 1 diabetes, suggesting that GAD65Ab phenotypes may be associated with different underlying pathogenic processes. The aim of this study was to test the hypothesis that Type 1 diabetes patients (n = 243; group I), GAD65Ab-positive healthy individuals (n = 28; group II), and healthy first-degree relatives of Type 1 diabetes patients (n = 41; group III) have antibody phenotypes that recognize different GAD65 epitopes. Sera from groups I-III were tested for their binding to GAD65 and GAD67, as well as six... (More)
Autoantibodies against the smaller isoform of glutamic acid decarboxylase (GAD) are markers for Type 1 diabetes. GAD65 autoantibody (GAD65Ab)-positive individuals in the general population are, however, mostly at low risk of developing Type 1 diabetes, suggesting that GAD65Ab phenotypes may be associated with different underlying pathogenic processes. The aim of this study was to test the hypothesis that Type 1 diabetes patients (n = 243; group I), GAD65Ab-positive healthy individuals (n = 28; group II), and healthy first-degree relatives of Type 1 diabetes patients (n = 41; group III) have antibody phenotypes that recognize different GAD65 epitopes. Sera from groups I-III were tested for their binding to GAD65 and GAD67, as well as six different GAD65/67 fusion proteins. Regardless of group, sera reactive to both GAD65 and GAD67 showed broader epitope reactivity than GAD65-specific sera. Furthermore, Type 1 diabetes patients showed a more restricted epitope binding than healthy individuals and first-degree relatives, demonstrating significantly less binding to the N-terminal part of GAD65 and to GAD67. Our analysis demonstrates that the N-terminal part is essential for full antibody binding to GAD65, in particular, to the middle epitope. It is suggested that Type 1 diabetes is associated with restricted GAD65Ab epitope specificity.
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- author
- Hampe, Christiane S ; Hammerle, Lisa P ; Bekris, Lynn ; Örtqvist, Eva ; Kockum, Ingrid ; Rolandsson, Olov ; Landin-Olsson, Mona LU ; Torn, Carina LU ; Persson, Bengt and Lernmark, Åke LU
- publishing date
- 2000
- type
- Contribution to journal
- publication status
- published
- in
- Journal of Clinical Endocrinology and Metabolism
- volume
- 85
- issue
- 12
- pages
- 9 pages
- publisher
- Oxford University Press
- external identifiers
-
- scopus:17744387308
- pmid:11134126
- ISSN
- 0021-972X
- DOI
- 10.1210/jc.85.12.4671
- language
- English
- LU publication?
- no
- id
- 43de39c0-35ea-4b03-999e-572a359f7147
- date added to LUP
- 2017-09-07 08:50:34
- date last changed
- 2024-04-28 19:22:07
@article{43de39c0-35ea-4b03-999e-572a359f7147, abstract = {{<p>Autoantibodies against the smaller isoform of glutamic acid decarboxylase (GAD) are markers for Type 1 diabetes. GAD65 autoantibody (GAD65Ab)-positive individuals in the general population are, however, mostly at low risk of developing Type 1 diabetes, suggesting that GAD65Ab phenotypes may be associated with different underlying pathogenic processes. The aim of this study was to test the hypothesis that Type 1 diabetes patients (n = 243; group I), GAD65Ab-positive healthy individuals (n = 28; group II), and healthy first-degree relatives of Type 1 diabetes patients (n = 41; group III) have antibody phenotypes that recognize different GAD65 epitopes. Sera from groups I-III were tested for their binding to GAD65 and GAD67, as well as six different GAD65/67 fusion proteins. Regardless of group, sera reactive to both GAD65 and GAD67 showed broader epitope reactivity than GAD65-specific sera. Furthermore, Type 1 diabetes patients showed a more restricted epitope binding than healthy individuals and first-degree relatives, demonstrating significantly less binding to the N-terminal part of GAD65 and to GAD67. Our analysis demonstrates that the N-terminal part is essential for full antibody binding to GAD65, in particular, to the middle epitope. It is suggested that Type 1 diabetes is associated with restricted GAD65Ab epitope specificity.</p>}}, author = {{Hampe, Christiane S and Hammerle, Lisa P and Bekris, Lynn and Örtqvist, Eva and Kockum, Ingrid and Rolandsson, Olov and Landin-Olsson, Mona and Torn, Carina and Persson, Bengt and Lernmark, Åke}}, issn = {{0021-972X}}, language = {{eng}}, number = {{12}}, pages = {{4671--4679}}, publisher = {{Oxford University Press}}, series = {{Journal of Clinical Endocrinology and Metabolism}}, title = {{Recognition of glutamic acid decarboxylase (GAD) by autoantibodies from different GAD antibody-positive phenotypes}}, url = {{http://dx.doi.org/10.1210/jc.85.12.4671}}, doi = {{10.1210/jc.85.12.4671}}, volume = {{85}}, year = {{2000}}, }