2 236

Cited 0 times in

Anti-GAD monoclonal antibody delays the onset of diabetes mellitus in NOD mice.

Authors
Menard, V; Jacobs, H; Jun, HS; Yoon, JW; Kim, SW
Citation
Pharmaceutical research, 16(7):1059-1066, 1999
Journal Title
Pharmaceutical research
ISSN
0724-87411573-904X
Abstract
Insulin Dependent Diabetes Mellitus (IDDM type I) is the result of autoimmune destruction of insulin producing pancreatic beta-cells by the cellular immune system, specifically, autoreactive T cells. Disease progression is evident by multiple autoantibodies responding to self-antigens in a cascade mechanism, wherein the first self-antigen induces the activation of the immune system, leading to the destruction of beta-cells and consequently, exposure of other antigens. Glutamic Acid Decarboxylase (GAD) is recognized in the literature as a primary autoantigen involved in the cascade. We questioned the immunological involvement of this autoantigen in the overall progression of the disease, specifically if antigen recognition by the cellular immune system (T cells) is necessary for organ specific autoimmunity and cellular toxicity. We tested this hypothesis by isolating, purifying and injecting monoclonal antibodies against GAD (anti-GAD Ab; 0.1 mg or 0.3 mg) into non-obese diabetic (NOD) mice on a weekly basis. We suggest that the anti-GAD Ab will bind to the GAD antigen, or perhaps bind to the epitope presented in association with APC-MHC and prevent T cell recognition, thereby delaying disease onset. Our results demonstrate a delay in the onset of diabetes and a decrease in the severity of insulitis in our test animals, when compared to controls. The mechanism of action of the anti-GAD Ab may be associated with a passive protection mechanism, as evidenced by the fact that splenocytes transferred from anti-GAD Ab treated mice did not prevent or delay diabetes in syngeneic irradiated NOD mice. The mechanism of diabetes prevention by administration of anti-GAD antibody could be associated with an interference in recognition of GAD by T cells, and continuing research will be perform to investigate this hypothesis.
MeSH terms
AnimalsAntibodies, Monoclonal/therapeutic use*Antibody SpecificityCell TransplantationDiabetes Mellitus, Type 1/immunology*Diabetes Mellitus, Type 1/prevention & control*FemaleGlutamate Decarboxylase/immunology*Immunization, Passive*Islets of Langerhans/immunologyMaleMiceMice, Inbred BALB CMice, Inbred NODSpleen/cytologySpleen/immunologySpleen/transplantationTransplantation Immunology
PMID
10450931
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
AJOU Authors
윤, 지원
Full Text Link
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse