GAD antibodies

Indication

Suspicion of type 1 diabetes (T1D), previously known as insulin-dependent diabetes mellitus (IDDM). Antibodies against GAD may also be associated to neurological diseases like Stiff Person Syndrome, Limbic Encephalitis, epilepsy, and cerebellar ataxia..

Method

Serum samples: ELISA, immunoblot and indirect immunofluorescence (IIF)

CSF samples:  Immunoblot and Indirect immunofluorescence (IIF)

Immunoblot and IIF are accredited analysis for serum samples – read more at the Quality page.

Answer

Serum samples are reported as negative or positive with a value.

CSF samples are reported as negative or positive.

Interpretation

There are two isoforms of GAD with molecular weight of 65 kDa and 67 kDa. GAD-65 is primarily expressed in pancreas while both GAD-65 and GAD-67 are expressed in the CNS.

IgG-antibodies against GAD occurs in serum in type 1 diabetes (T1D) and is detected in approximately 70-80% of young newly diagnosed persons. If, at the same time there are antibodies to islet cells, ?-cell antigen 2 (IA-2), insulin (IAA) and zinc transporter 8, it strengthens the diagnosis. Antibodies can be detected before clinical signs of T1D. Slightly elevated values may also occur in other autoimmune endocrine disorders, especially autoimmune thyroiditis.

Anti-GAD antibodies also occur in 60% of patients with Stiff Person Syndrome and have been observed in both serum and CSF. Anti-GAD antibodies may also be associated with limbic encephalitis, epilepsy, and cerebellar ataxia. Association to cancer is unusual but has been reported at several different cancer forms (breast-, small cell lung cancer, endocrine tumors). Patients with neurological symptoms often have much higher titer of anti-GAD antibodies compared to patients with T1D.

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References

Falorni A, Kockum I, Sanjeevi C.B and Lernmark A. (1995). Pathogenesis of insulindependent diabetes mellitus. Baillieres.Clin.Endocrinol.Metab. 9, 25-46.

Hagopian W.A, Sanjeevi C.B, Kockum I, Landin Olsson M, Karlsen A.E, Sundkvist G, Dahlquist G, Palmer J and Lernmark A. (1995). Glutamate decarboxylase-, insulin-, and islet cell-antibodies and HLA typing to detect diabetes in a general population-based study of Swedish children. J.Clin.Invest.95, 1505-1511.

Rorsman F, Husebye E.S, Winqvist O, Bjork E, Karlsson F.A and Kampe O. (1995). Aromatic-L-amino-acid  decarboxylase, a pyrodoxal phosphate-dependent enzyme, is a betacell autoantigen. Proc.Natl.Acad.Sci.U.S:A. 92, 8626-8629.

Zimmet P.Z. (1995). The pathogenesis and prevention of diabetes in adults. Genes, autoimmunity, and demography. Diabetes.Care, 18, 1050-1064.

Lernmark Ă…. Type I diabetes. Clin Chem 1999, 45, 1331-1338.

Kulmala et al. Prediction of insulin-dependent diabetes mellitus in siblings of children with diabetes. J Clin Invest 1998, 101, 327-336.

Verge et al. Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, IA-2 autoantibodies. Diabetes 1996, 45, 926-933.

Turner et al. UKPDS25: autoantibodies to islet cell cytoplasm and GAD for prediction of insulin requirement in type 2 diabetes. Lancet, 1997,350, 1288-1259.

Merger et al. The broad clinical phenotype of Type 1 diabetes at presentation. Diabet Med. 2013 Feb;30(2):170-8.

Saiz et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain. 2008 Oct;131(Pt 10):2553-2563. PMID 18687732

Vincent. Stiff, twitchy or wobbly—are GAD antibodies pathogenic? Brain. 2008. 131 (10): 2536-2537.

Accredited analysis – read more at the Quality page.

Packages and other tests

View other packages Diabetes (531), Lambert-Eatons myastena syndrom (LEMS) (563), Paraneoplastic Syndromes and Limbic Encephalitis (560, 561 and 562), Stiff person syndrome/PERM (568). View other tests Amphiphysin antibodies, Glycine receptor (GlyR) antibodies, IA-2 antibodies, Insulin antibodies, Islet cell antibodies

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