INDIVIDUAL TEST 089

GAD Antibodies

Indication

Suspicion of type 1 diabetes (T1D). Antibodies against GAD may also be associated with neurological diseases like Stiff Person Syndrome, Limbic Encephalitis, epilepsy, and cerebellar ataxia.

Sample material

Serum

• Minim. volume: 0,5 mL

CSF

• Minim. volume: 2,0 mL

Transport

Within Sweden

• room temperature

International

• cold

Method

Serum

• ELISA, Immunoblot and Indirect immunofluorescence (IIF)

CSF

• Immunoblot and Indirect immunofluorescence (IIF)

According to guidelines Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes, anti-neuronal antibodies should be detected by at least two independent methods to be reliable. At Wieslab, IIF and immunoblot are used.

Reference interval

Serum

• ELISA: <10 IU/mL negative
• Immunoblot: <5 negative
• Indirect Immunofluorescence: <1:10 negative

CSF

• Immunoblot: negative
• Indirect immunofluorescence: negative

Result

Serum

• ELISA: results are reported as negative, borderline, or positive with a concentration (IU/mL).
• Immunoblot: results are reported as negative, borderline, or positive with an intensity value.
• Indirect immunofluorescence (IIF): results are reported as negative or positive. Positive results will be titrated.

CSF

• Immunoblot: Results are reported as negative, borderline, or positive.
• Indirect immunofluorescence(IIF): Results are reported as negative or positive.

Interpretation

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

IgG-antibodies against GAD occur in serum in type 1 diabetes (T1D) and are detected in approximately 70-80% of the cases. The antibodies can often be detected prior to diagnosis. Simultaneous presence of antibodies against islet cells, ß-cell antigen 2 (IA-2), insulin (IAA), and zinc transporter 8, strongly indicate manifestation or future development of T1D.

A slight increase of anti-GAD antibodies can be present during other autoimmune endocrine diseases, especially autoimmune thyroiditis.

Anti-GAD antibodies occur in 60% of patients with Stiff Person Syndrome and can then be detected in both serum and CSF. Anti-GAD antibodies may also be associated with limbic encephalitis, epilepsy, and cerebellar ataxia. Association with cancer is unusual but has been reported in conjunction with breast-, small-cell lung cancer, and endocrine tumors.

Antibodies against GAD-65 are graded as Lower-risk antibodies with a frequency of <15% of underlying cancer and a positive result yields 0 points PNS score, according to Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes.

References

• Merger SR et al. Diabet Med. 2013. The broad clinical phenotype of Type 1 diabetes at presentation. PMID: 23075321
• Saiz A et al. Brain. 2008. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. PMID: 18687732
• Vincent A. Brain. 2008. Stiff, twitchy or wobbly: are GAD antibodies pathogenic? PMID: 18799517
• Lancaster E et al. Neurology. 2011. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. PMID: 21747075
• Balint B et al. Brain. 2018. Movement disorders with neuronal antibodies: syndromic approach, genetic parallels and pathophysiology. PMID: 29053777
• Graus F et al. Neurol Neuroimmunol Neuroinflamm. 2021. Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes. PMID: 34006622
• Zuliani L et al. J Neurol Neurosurg Psychiatry. 2012. Central nervous system neuronal surface antibody associated syndromes: review and guidelines for recognition. PMID: 22448032
• Rosenfeld MR, Dalmau J. Neurol Clin. 2018. Paraneoplastic Neurologic Syndromes. PMID: 30072076
• Scheper T et al, EUROLINE_WB allows reliable differentiation of autoantibodies against neural antigens in patients with paraneoplastic neurological syndrome, In: “From proteinomic to Molecular Epidemiology: Relevance of Autoantibodies”, 6th Dresden Symposium on Autoantibodies. 2002, Vol 3, 562-563
• Garza M, Piquet AL. Front Neurol. 2021. Update in Autoimmune Movement Disorders: Newly Described Antigen Targets in Autoimmune and Paraneoplastic Cerebellar Ataxia. PMID: 34489848

Last updated: 2024-06-26