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Modulation of diabetes in NOD mice by GAD65‐specific monoclonal antibodies is epitope specific and accompanied by anti‐idiotypic antibodies
Author(s) -
Hall Tyler R.,
Bogdani Marika,
LeBoeuf Renee C.,
Kirk Elizabeth A.,
Maziarz Marlena,
Banga J. Paul,
Oak Shilpa,
Pennington Christina A.,
Hampe Christiane S.
Publication year - 2008
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2007.02724.x
Subject(s) - epitope , nod , monoclonal antibody , antibody , nod mice , autoantibody , immunology , idiotype , autoimmune disease , glutamate decarboxylase , autoimmunity , medicine , diabetes mellitus , biology , endocrinology , enzyme , biochemistry
Summary 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 b96·11 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.