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GAD65 Autoimmunity-Clinical Studies

Uibo, Raivo and Lernmark, Åke LU (2008) In Advances in Immunology 100. p.39-78
Abstract
Type 1 diabetes (TID) in children and particularly in teenagers and adults is strongly associated with autoreactivity to the Mr 65,000 isoform of glutamic acid decarboxylase (GAD65). Autoantibodies to GAD65 are common at the time of clinical diagnosis and may be present for years prior to the onset of hyperglycemia. GAD65 autoantibodies predict conversion to insulin dependence when present in patients classified with type 2 diabetes nowadays more often referred to as patients with latent autoimmune diabetes in the adult (LADA) or type 1,5 diabetes. Analyses of T cells with HLA DRB1*0401-tetramers with GAD65-specific peptides as well as of anti-idiotypic GAD65 autoantibodies suggest that GAD6S auto-reactivity is common. The immunological... (More)
Type 1 diabetes (TID) in children and particularly in teenagers and adults is strongly associated with autoreactivity to the Mr 65,000 isoform of glutamic acid decarboxylase (GAD65). Autoantibodies to GAD65 are common at the time of clinical diagnosis and may be present for years prior to the onset of hyperglycemia. GAD65 autoantibodies predict conversion to insulin dependence when present in patients classified with type 2 diabetes nowadays more often referred to as patients with latent autoimmune diabetes in the adult (LADA) or type 1,5 diabetes. Analyses of T cells with HLA DRB1*0401-tetramers with GAD65-specific peptides as well as of anti-idiotypic GAD65 autoantibodies suggest that GAD6S auto-reactivity is common. The immunological balance is disturbed and the appearance of GAD65 autoantibodies represents markers of autoreactive loss of pancreatic beta cells. Extensive experimental animal research. in particular of the Non-obese diabetic (NOD) mouse, showed that GAD65 therapies reduce insulitis and prevent spontaneous diabetes. Recombinant human GAD65 produced by current Good Manufacturing Practice (cGMP) and formulated with alum was found to be safe in Phase I and 11 placebo-controlled, double-blind, randomized clinical trials. The approach to modulate GAD65 autoreactivity with subcutaneous immunotherapy (SCIT) showed promise as alum-formulated GAD65 induced a dose-dependent reduction in the disappearance rate of endogenous residual C-peptide production. Additional controlled clinical trials are needed to uncover the mechanisms by which subcutaneous injections of recombinant human GAD65 may alter GAD6S autoreactivity. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Advances in Immunology
volume
100
pages
39 - 78
publisher
Elsevier
external identifiers
  • wos:000261945700003
  • scopus:57749203195
ISSN
0065-2776
DOI
10.1016/S0065-2776(08)00803-1
language
English
LU publication?
yes
id
5cb581d7-2c42-4551-b4a0-7df9053e50fb (old id 1376278)
date added to LUP
2009-04-24 12:31:18
date last changed
2017-09-24 03:59:42
@article{5cb581d7-2c42-4551-b4a0-7df9053e50fb,
  abstract     = {Type 1 diabetes (TID) in children and particularly in teenagers and adults is strongly associated with autoreactivity to the Mr 65,000 isoform of glutamic acid decarboxylase (GAD65). Autoantibodies to GAD65 are common at the time of clinical diagnosis and may be present for years prior to the onset of hyperglycemia. GAD65 autoantibodies predict conversion to insulin dependence when present in patients classified with type 2 diabetes nowadays more often referred to as patients with latent autoimmune diabetes in the adult (LADA) or type 1,5 diabetes. Analyses of T cells with HLA DRB1*0401-tetramers with GAD65-specific peptides as well as of anti-idiotypic GAD65 autoantibodies suggest that GAD6S auto-reactivity is common. The immunological balance is disturbed and the appearance of GAD65 autoantibodies represents markers of autoreactive loss of pancreatic beta cells. Extensive experimental animal research. in particular of the Non-obese diabetic (NOD) mouse, showed that GAD65 therapies reduce insulitis and prevent spontaneous diabetes. Recombinant human GAD65 produced by current Good Manufacturing Practice (cGMP) and formulated with alum was found to be safe in Phase I and 11 placebo-controlled, double-blind, randomized clinical trials. The approach to modulate GAD65 autoreactivity with subcutaneous immunotherapy (SCIT) showed promise as alum-formulated GAD65 induced a dose-dependent reduction in the disappearance rate of endogenous residual C-peptide production. Additional controlled clinical trials are needed to uncover the mechanisms by which subcutaneous injections of recombinant human GAD65 may alter GAD6S autoreactivity.},
  author       = {Uibo, Raivo and Lernmark, Åke},
  issn         = {0065-2776},
  language     = {eng},
  pages        = {39--78},
  publisher    = {Elsevier},
  series       = {Advances in Immunology},
  title        = {GAD65 Autoimmunity-Clinical Studies},
  url          = {http://dx.doi.org/10.1016/S0065-2776(08)00803-1},
  volume       = {100},
  year         = {2008},
}