The lack of anti-idiotypic antibodies, not the presence of the corresponding autoantibodies to glutamate decarboxylase, defines type 1 diabetes
(2008) In Proceedings of the National Academy of Sciences 105(14). p.5471-5476- Abstract
- Autoantibodies to glutamate decarboxylase 65 (GAD65Ab) are commonly believed to be a major characteristic for type 1 diabetes (T1D). We investigated the presence of GAD65Ab in healthy individuals (n = 238) and first-degree relatives (FDRs) of T1D patients (n = 27) who tested negative for GAD65Ab in conventional RIAs. Sera were applied to affinity columns coated with GAD65-specific mAbs to absorb anti-idiotypic antibodies (anti-Ids). The absorbed sera were analyzed for binding to GAD65 by RIAs. Both healthy individuals and FDRs present GAD65Ab that are inhibited by anti-Id, masking them in conventional detection methods. The presence of GAD65Ab-specific anti-Ids was confirmed by competitive ELISA. Remarkably, T1D patients (n = 54) and Stiff... (More)
- Autoantibodies to glutamate decarboxylase 65 (GAD65Ab) are commonly believed to be a major characteristic for type 1 diabetes (T1D). We investigated the presence of GAD65Ab in healthy individuals (n = 238) and first-degree relatives (FDRs) of T1D patients (n = 27) who tested negative for GAD65Ab in conventional RIAs. Sera were applied to affinity columns coated with GAD65-specific mAbs to absorb anti-idiotypic antibodies (anti-Ids). The absorbed sera were analyzed for binding to GAD65 by RIAs. Both healthy individuals and FDRs present GAD65Ab that are inhibited by anti-Id, masking them in conventional detection methods. The presence of GAD65Ab-specific anti-Ids was confirmed by competitive ELISA. Remarkably, T1D patients (n = 54) and Stiff Person Syndrome patients (n = 8) show a specific lack of anti-Ids to disease-associated GAD65Ab epitopes. Purified anti-Ids from healthy individuals and FDRs inhibited the binding of GAD65Ab from T1D patients to GAD65. We conclude that masked GAD65Ab are present in the healthy population and that a lack of particular anti-Ids, rather than GAD65Ab per se, is a characteristic of T1D. The lack of these inhibitory antibodies may contribute to T cell activation by GAD65Ab. (Less)
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https://lup.lub.lu.se/record/1205639
- author
- Oak, Shilpa ; Gilliam, Lisa K. ; Landin-Olsson, Mona LU ; Törn, Carina LU ; Kockum, Ingrid ; Pennington, Christina R. ; Rowley, Merrill J. ; Christie, Michael R. ; Banga, J. Paul and Hampe, Christiane S.
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Proceedings of the National Academy of Sciences
- volume
- 105
- issue
- 14
- pages
- 5471 - 5476
- publisher
- National Academy of Sciences
- external identifiers
-
- wos:000254893600035
- scopus:44449135894
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.0800578105
- language
- English
- LU publication?
- yes
- id
- a44a065f-d4cc-454f-be88-d92d8064f389 (old id 1205639)
- date added to LUP
- 2016-04-01 11:46:50
- date last changed
- 2024-02-23 07:41:09
@article{a44a065f-d4cc-454f-be88-d92d8064f389, abstract = {{Autoantibodies to glutamate decarboxylase 65 (GAD65Ab) are commonly believed to be a major characteristic for type 1 diabetes (T1D). We investigated the presence of GAD65Ab in healthy individuals (n = 238) and first-degree relatives (FDRs) of T1D patients (n = 27) who tested negative for GAD65Ab in conventional RIAs. Sera were applied to affinity columns coated with GAD65-specific mAbs to absorb anti-idiotypic antibodies (anti-Ids). The absorbed sera were analyzed for binding to GAD65 by RIAs. Both healthy individuals and FDRs present GAD65Ab that are inhibited by anti-Id, masking them in conventional detection methods. The presence of GAD65Ab-specific anti-Ids was confirmed by competitive ELISA. Remarkably, T1D patients (n = 54) and Stiff Person Syndrome patients (n = 8) show a specific lack of anti-Ids to disease-associated GAD65Ab epitopes. Purified anti-Ids from healthy individuals and FDRs inhibited the binding of GAD65Ab from T1D patients to GAD65. We conclude that masked GAD65Ab are present in the healthy population and that a lack of particular anti-Ids, rather than GAD65Ab per se, is a characteristic of T1D. The lack of these inhibitory antibodies may contribute to T cell activation by GAD65Ab.}}, author = {{Oak, Shilpa and Gilliam, Lisa K. and Landin-Olsson, Mona and Törn, Carina and Kockum, Ingrid and Pennington, Christina R. and Rowley, Merrill J. and Christie, Michael R. and Banga, J. Paul and Hampe, Christiane S.}}, issn = {{1091-6490}}, language = {{eng}}, number = {{14}}, pages = {{5471--5476}}, publisher = {{National Academy of Sciences}}, series = {{Proceedings of the National Academy of Sciences}}, title = {{The lack of anti-idiotypic antibodies, not the presence of the corresponding autoantibodies to glutamate decarboxylase, defines type 1 diabetes}}, url = {{http://dx.doi.org/10.1073/pnas.0800578105}}, doi = {{10.1073/pnas.0800578105}}, volume = {{105}}, year = {{2008}}, }