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, borderline or positive with a value.

CSF samples are reported as negative, borderline or positive.

Interpretation

There are two isoforms of GAD (65 kDa and 67 kDa). GAD-65 is primarily expressed in pancreas while both GAD-65 and GAD-67 are expressed in the CNS. In type 1 diabetes occurs antibodies against GAD-65, while both specificities of antibodies can be demonstrated in the neurological condition. Patients with neurological symptoms often have much higher titer of anti-GAD antibodies compared to patients with T1D.

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).

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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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