Summary
The role of anti-glutamic acid decarboxylase (GAD) 65 autoantibodies in autoimmune
neurological conditions is evolving, but testing recommendations remain unchanged
in Australia with GAD enzyme-linked immunosorbent assay (ELISA) and immunoblot as
the only two Therapeutic Goods Administration approved testing methods available in
Australia. Common practice is for use of ELISA in diagnosis of type 1 diabetes mellitus
(T1DM) and use of immunoblot for diagnosis of GAD65-associated neurological disease.
We observed a cohort of patients with negative immunoblot results and positive ELISA
in the context of GAD-associated neurological disease without T1DM. In the absence
of robust consensus guidelines on preferred testing modalities, we sought to determine
if ELISA could have a superior role in the diagnosis of GAD-associated neurological
disease when compared to immunoblot in this paper.
We tested for anti-GAD65 autoantibodies on 55 patient samples, 40 samples requested
for neurological disease and 15 type 1 diabetes samples with detectable anti-GAD65,
using two testing platforms: Euroimmun anti-GAD enzyme-linked immunosorbent assay
(ELISA) and.
Euroimmun EuroLine immunoblot for paraneoplastic neurologic syndromes. These results
were correlated against the clinical scenario.
Positive ELISA results had a sensitivity of 100% and specificity of 91% for GAD65-related
neurological disease. Immunoblot showed sensitivity of 43% and specificity of 76%
for GAD65-related neurological disease. ELISA proved more sensitive and specific for
GAD65-related neurological disease compared to immunoblot, raising questions about
the role of this testing modality in neurological disease. We propose that ELISA should
be used as a sole diagnostic method for all GAD65 antibody-related neurological disease
over immunoblot. The presence of anti-GAD65 antibody on immunoblot is of doubtful
clinical significance.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to PathologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Autoantibodies to synaptic receptors and neuronal cell surface proteins in autoimmune diseases of the central nervous system.Physiol Rev. 2017; 97: 839-887
- Cerebellar ataxia and glutamic acid decarboxylase antibodies: immunologic profile and long-term effect of immunotherapy.JAMA Neurol. 2014; 71: 1009-1016
- Autoimmunity to glutamic acid decarboxylase (GAD) in stiff-man syndrome and insulin-dependent diabetes mellitus.Trends Neurosci. 1991; 14: 452-457
- Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus.N Engl J Med. 1988; 318: 1012-1020
- Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis.Ann Neurol. 2010; 67: 470-478
- Cerebellar ataxia associated with anti-glutamic acid decarboxylase autoantibodies.Cerebellum. 2003; 2: 77-79
- Two human glutamate decarboxylases,65-kDa GAD and 67-kDa GAD, are each encoded by a single gene.Proc Natl Acad Sci USA. 1992; 89: 2115-2119
- Detection of recombinant GAD65 and GAD67 antibodies using a simple radioimmunoassay.Diabetes Res Clin Pract. 1996; 32: 61-69
- Autoantibodies against GAD65 rather than GAD67 precede the onset of type 1 diabetes.Autoimmunity. 1994; 19: 71-80
- Identification of the 64 K autoantigen in insulin-dependant diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase.Nature. 1990; 347: 151-156
- Neurologic disorders associated with anti-glutamic acid decarboxylase antibodies: a comparison of anti-GAD antibody titres and time-dependant changes between neurologic disease and type 1 diabetes mellitus.J Neuroimmunol. 2018; 317: 84-89
- Higher autoantibody levels and recognition of a linear NH2 - terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependant diabetes mellitus.J Exp Med. 1994; 180: 595-606
- Neurologic syndromes related to anti-GAD65: clinical and serologic response to treatment.Neurol Neuroimmunol Neuroinflamm. 2020; 7: 1-13
- Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies.Neurology. 2001; 57: 780-784
- Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association.Brain. 2008; 131: 2553-2563
- GAD antibodies in neurological disorders – insights and challenges.Nature. 2020; 16: 353-365
Article info
Publication history
Published online: April 08, 2023
Accepted:
January 14,
2023
Received in revised form:
December 23,
2022
Received:
June 21,
2022
Identification
Copyright
© 2023 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.
