Glutamic acid decarboxylase antibodies

This situation is largely due to the rise of type 2 DM which now accounts for 85-90% of all cases of DM type 1 DM in which antibodies directed at the enzyme glutamic acid decarboxylase (GAD) attack and destroy the insulin-producing (3 cells... 

In three middle-aged patients, diabetes was diagnosed after 3-7 months of treatment with interferon alfa-2b and ribavirin, and two presented with severe ketoacidosis (534,535). There was a family history of diabetes in one patient and two had high titers of glutamic acid decarboxylase antibodies before treatment. One patient never had diabetes-related serum autoantibodies before or after interferon alfa therapy. All three required permanent insulin treatment despite withdrawal of interferon alfa. 

In a randomized trial in 74 patients with chronic hepatitis C treated with interferon alfa-2b and ribavirin, plus placebo or amantadine, two developed glutamic acid decarboxylase (GAD) autoantibodies, but none developed IA-2 or insulin autoantibodies (543). One had an increased titer of GAD autoantibodies during a first sequence of interferon alfa monotherapy, then a further rise during subsequent combination therapy, and finally developed diabetes mellitus after 5 months of treatment. The authors suggested that repetitive treatment with interferon alfa could increase the risk of type 1 diabetes in patients previously positive for islet antibodies. 

The exact mechanisms of tacrolimus-induced diabetes are unknown. In one renal transplant patient with genetic susceptibility, tacrolimus was associated with insulin-dependent diabetes mellitus and the simultaneous occurrence of anti-glutamic acid decarboxylase antibody (1096). Within 2 months after conversion from tacrolimus to ciclosporin, the antibody was no longer detected and the patient s insulin requirements fell dramatically. Tacrolimus-induced direct beta cell toxicity, with... 

Yoshioka K, Sato T, Okada N, Ishii T, Imanishi M, Tanaka S, Kim T, Sugimoto T, Fujii S. Post-transplant diabetes with anti-glutamic acid decarboxylase antibody during tacrolimus therapy. Diabetes Res Clin Pract 1998 42(2) 85-9. 

Antibodies to islet cells, insulin, and glutamic acid decarboxylase are present in many patients with newly diagnosed type 1 diabetes. In... 

The most definitive laboratory test to distinguish type 1 from type 2 diabetes is the C-peptide assay, which is a measure of endogenous insulin production. With type 2 diabetes, proinsulin can be split into insulin and C-peptide lack of C-peptide indicates type 1 diabetes. The presence of anti-islet antibodies (to glutamic acid decarboxylase, insulinoma associated peptide-2 or insulin) or absence of insulin resistance (determined by a glucose tolerance test) is also suggestive of type 1. 

In this case, which was marked by three autoimmune complications (insulin-dependent diabetes mellitus, myositis, and myasthenia gravis) in a single patient, a retrospective analysis of the patient s serum before aldesleukin therapy showed the presence of antibodies against glutamic acid decarboxylase, insulin, islet cell antigen, and striated muscle, but was negative for acetylcholine receptor antibodies. Immune stimulation by aldesleukin was... 

A 32-year-old woman with previous autoimmune disorders and a susceptible HLA haplotype developed diabetes with newly positive glutamic acid decarboxylase antibody after taking tacrolimus for 5 months (43). 

Schmidh RS, Colman PG, Bonifacio E. Disease sensitivity and specificity of 52 assays for glutamic acid decarboxylase antibodies. The Second International GADAB Workshop. Diabetes 1995 44 636-40. 

Fig. 9. Aspartate aminotransferase immunoreactivity in glutamic acid decarboxylase (GAD)-immunoreactive neuronal processes in the cerebral cortex. sAAT but not mAAT is colocalized with GAD in fine, probably axonal processes (arrows). Rat sections were double-immunostained by incubation with a mixture of anti-sAAT or mAAT rabbit serum and anti-GAD sheep serum, then with biotinylated anti-rabbit IgG donkey antibody, and finally with Texas Red-conjugated avidin and fluorescein-labeled anti-sheep IgG donkey antibody. The photographs in each row were taken at the same site under different excitations. Asterisks in (a) and (o ) indicate the unlabeled cell body of a pyramidal neuron.

Vianello M, Tavolato B, Giometto B (2002) Glutamic acid decarboxylase antibodies and neurological disorders. Neurol Sci 23 145-151. 

Chang Y-C, Gottlieb D1 (1988) Characterization of the proteins purified with monoclonal antibodies to glutamic acid decarboxylase. J. Neurosci, 8, 2123-2130. 

Oertel WH, Schmechel DE, Tappaz ML, Kopin IJ (1981a) Production of a specific antiserum to rat brain glutamic acid decarboxylase by injection of an antigen-antibody complex. Neuroscience, 6, 2689-2700. 

Langer P, Tajtakova M, Guretzki HJ, Kocan A, Petrik J, Chovancova J, Drobna B, Jursa S, Pavuk M, Tmovec T, Sebokova E, Klimes I (2002) High prevalence of anti-glutamic acid decarboxylase (anti-GAD) antibodies in employees at a polychlorinated biphenyl production factory. Arch Environ Health, 57(5) 412-415. 

Cao, C., and Sim, SJ. (2007) Signal enhancement of surface plasmon resonance immunoassay using enzyme precipitation functionalized gold nanoparticles a femto molar level measurement of anti glutamic acid decarboxylase antibody. Biosensors and Bioelectronics, 22, 1874 1880. 

An assay for diagnosing type I diabetes mellitus based on the detection of anti-glutamic acid decarboxylase (GAD) antibodies in buffer by a Biacore 2000, is presented in [47,48]. Biotinylated GAD was immobihzed on a streptavidin-coated surface. The effect of mixed SAM composition (differing in ratios of hydroxyl- and carboxyl-terminated alkanethiols) on the sensitivity of the sensor was investigated. On SPR sensor chips prepared with the optimized SAM composition (10 1 ratio of 3-mercaptopropanol to 11-mercaptoundecanoic acid), a concentration of anti-GAD as low as... 

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