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: ELISA, immunoblot and indirect immunofluorescence (IIF)
CSF: Immunoblot and Indirect immunofluorescence (IIF)
According to guidelines, anti-neuronal antibodies should be detected by at least two independent methods. At Wieslab IIF and immunoblot are used. According to European guidelines, a positive result should be obtained with both methods to be reliable
Result 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).
Antibodies against GAD-65 are graded as Lower-risk antibodies with a frequency of <15% of underlying cancer and a positive result yield 0 points PNS score, according to Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes.
References
- 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.
- Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology. 2011 Jul 12;77(2):179-89. PMID: 21747075
- Balint B, Vincent A, Meinck HM, Irani SR, Bhatia KP. Movement disorders with neuronal antibodies: syndromic approach, genetic parallels and pathophysiology. Brain. 2018 Jan 1;141(1):13-36. PMID: 29053777
- Graus F, et al. Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes. Neurol Neuroimmunol Neuroinflamm. 2021 May 18;8(4):e1014. PMID: 34006622
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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 Serum: ELISA, immunoblot och indirekt immunofluorescens (IIF)
Likvor: Immunoblot och indirekt immunofluorescens (IIF)
Enligt riktlinjer ska anti-neuronala antikroppar detekteras med minst två oberoende metoder. På Wieslab används IIF och immunoblot. Enligt europeiska riktlinjer ska positivt resultat uppnås med båda metoderna för att vara tillförlitligt.
Svar Serumprov rapporteras som negativt, gränsvärde eller positivt med värde.
Likvorprov rapporteras som negativt, gränsvärde eller positivt.
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).
Antikropparna riktade mot GAD-65 bedöms vara Lower-risk antibodies med en förekomst på <15 % för en underliggande cancer och positivitet ger 0 poäng i PNS score enligt Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes.
Referenser
- 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.
- Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology. 2011 Jul 12;77(2):179-89. PMID: 21747075
- Balint B, Vincent A, Meinck HM, Irani SR, Bhatia KP. Movement disorders with neuronal antibodies: syndromic approach, genetic parallels and pathophysiology. Brain. 2018 Jan 1;141(1):13-36. PMID: 29053777
- Graus F, et al. Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes. Neurol Neuroimmunol Neuroinflamm. 2021 May 18;8(4):e1014. PMID: 34006622
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