Modulation of diabetes in NOD mice by GAD65-specific monoclonal antibodies is epitope specific and accompanied by anti-idiotypic antibodies
(2008) In Immunology 123(4). p.547-554- Abstract
Type 1 diabetes is caused by the autoimmune destruction of pancreatic beta cells. Here we show that administration of a human monoclonal antibody (b96.11) specific to the 65-kDa isoform of glutamate decarboxylase (GAD65) to prediabetic non-obese diabetic (NOD) mice significantly delays the onset of autoimmune diabetes. We found this effect to be epitope-specific, as only b96.11 showed this therapeutic property, while a GAD65-specific human monoclonal control antibody (b78) derived from the same patient, but specific to a different determinant of GAD65, had no significant effect on the progression of disease. Administration of b96.1 or b78 to NOD mice was accompanied by the generation of anti-idiotypic antibodies. Importantly, the... (More)
Type 1 diabetes is caused by the autoimmune destruction of pancreatic beta cells. Here we show that administration of a human monoclonal antibody (b96.11) specific to the 65-kDa isoform of glutamate decarboxylase (GAD65) to prediabetic non-obese diabetic (NOD) mice significantly delays the onset of autoimmune diabetes. We found this effect to be epitope-specific, as only b96.11 showed this therapeutic property, while a GAD65-specific human monoclonal control antibody (b78) derived from the same patient, but specific to a different determinant of GAD65, had no significant effect on the progression of disease. Administration of b96.1 or b78 to NOD mice was accompanied by the generation of anti-idiotypic antibodies. Importantly, the induced anti-idiotypic antibodies were specific for the immunizing antibody and blocked the binding of GAD65 by the respective antibody. These findings suggest a potential role for the internal image of the GAD65 determinant recognized by b96.11 in the anti-idiotypic antibody, supporting an immunomodulatory role for GAD65-specific autoantibodies, as originally postulated by Jerne.
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- author
- Hall, Tyler R. ; Bogdani, Marika ; LeBoeuf, Renee C. ; Kirk, Elizabeth A. ; Maziarz, Marlena LU ; Banga, J. Paul ; Oak, Shilpa ; Pennington, Christina A. and Hampe, Christiane S.
- publishing date
- 2008-04-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Anti-idiotypic antibodies, Autoantibodies, Autoimmune diabetes, GAD65, NOD mouse
- in
- Immunology
- volume
- 123
- issue
- 4
- pages
- 8 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:18005036
- scopus:39549091299
- ISSN
- 0019-2805
- DOI
- 10.1111/j.1365-2567.2007.02724.x
- language
- English
- LU publication?
- no
- id
- eb590fb7-9f63-4774-ba4b-b99ff48f2a8c
- date added to LUP
- 2019-08-05 13:19:08
- date last changed
- 2024-03-19 18:34:52
@article{eb590fb7-9f63-4774-ba4b-b99ff48f2a8c,
abstract = {{<p>Type 1 diabetes is caused by the autoimmune destruction of pancreatic beta cells. Here we show that administration of a human monoclonal antibody (b96.11) specific to the 65-kDa isoform of glutamate decarboxylase (GAD65) to prediabetic non-obese diabetic (NOD) mice significantly delays the onset of autoimmune diabetes. We found this effect to be epitope-specific, as only b96.11 showed this therapeutic property, while a GAD65-specific human monoclonal control antibody (b78) derived from the same patient, but specific to a different determinant of GAD65, had no significant effect on the progression of disease. Administration of b96.1 or b78 to NOD mice was accompanied by the generation of anti-idiotypic antibodies. Importantly, the induced anti-idiotypic antibodies were specific for the immunizing antibody and blocked the binding of GAD65 by the respective antibody. These findings suggest a potential role for the internal image of the GAD65 determinant recognized by b96.11 in the anti-idiotypic antibody, supporting an immunomodulatory role for GAD65-specific autoantibodies, as originally postulated by Jerne.</p>}},
author = {{Hall, Tyler R. and Bogdani, Marika and LeBoeuf, Renee C. and Kirk, Elizabeth A. and Maziarz, Marlena and Banga, J. Paul and Oak, Shilpa and Pennington, Christina A. and Hampe, Christiane S.}},
issn = {{0019-2805}},
keywords = {{Anti-idiotypic antibodies; Autoantibodies; Autoimmune diabetes; GAD65; NOD mouse}},
language = {{eng}},
month = {{04}},
number = {{4}},
pages = {{547--554}},
publisher = {{Wiley-Blackwell}},
series = {{Immunology}},
title = {{Modulation of diabetes in NOD mice by GAD65-specific monoclonal antibodies is epitope specific and accompanied by anti-idiotypic antibodies}},
url = {{http://dx.doi.org/10.1111/j.1365-2567.2007.02724.x}},
doi = {{10.1111/j.1365-2567.2007.02724.x}},
volume = {{123}},
year = {{2008}},
}