INDIVIDUAL TEST 089

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 analyses for serum samples.

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).

ReferencesFalorni 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 Å. 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.

More information

This is an accredited test.
> Read more [.pdf]

Learn more about sampling.
> Read more

Download request forms

Autoimmune diagnostics
Neurology

ENSKILD ANALYS 089

GAD-antikroppar

Indikation Misstanke om diabetes typ 1 (T1D). Antikroppar mot GAD kan också vara associerade med limbisk encefalit, epilepsi och cerebellär ataxi.

Metod

Serumprov: ELISA, immunoblot och indirekt immunofluorescens (IIF)

Likvorprov: Immunoblot och indirekt immunofluorescens (IIF)

IIF och immunoblot-analys för serum är ackrediterade.

Svar

Serumprov rapporteras som negativt, gränsvärde eller positivt med värde. Likvorprov rapporteras som positivt, gränsvärde eller negativt.

Tolkning

Det finns två isoformer av GAD (65 kDa och 67 kDa). I bukspottskörteln uttrycks främst GAD-65 och i CNS uttrycks både GAD-65 och GAD-67. Vid typ 1 diabetes (T1D) förekommer antikroppar mot GAD-65 medan båda specificiteterna kan påvisas vid neurologiska tillstånd. Patienter med neurologiska symptom har ofta mycket högre nivå av anti-GAD antikroppar jämfört med patienter med T1D.

Anti-GAD-antikroppar förekommer hos ca 60% av patienterna med Stiff Person Syndrom och påvisas då i både serum och likvor. Anti-GAD antikroppar kan också vara associerade med limbisk encefalit, epilepsi och cerebellär ataxi. Association till cancer är ovanligt men rapporterats vid flera olika cancerformer (bröst-, småcellig lungcancer, endokrina tumörer).

Referenser

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 Å. 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.

Mer information

Detta är en ackrediterad analys.
> Läs mer [.pdf]

Mer information om provtagning.
> Läs mer

Ladda ner remiss

Autoimmun diagnostik
Neurologi