Effects of anti–glutamic acid decarboxylase antibodies associated with neurological diseases

Manto, Mario‐Ubaldo; Laute, Marie-Aline; Aguera, M.; Rogemond, Véronique; Pandolfo, Massimo; Honnorat, Jérôme

doi:10.1002/ana.21123

Cited by 235 publications

(189 citation statements)

References 37 publications

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“…This phenomenon was not observed after administration of IgG antibodies from T1D patients, which indicate that SPS could be the direct consequence of antibody-mediated neuronal dysfunction (Manto 2007). Also, electrophysiological studies have shown that CSF or serum positive for GAD65…”

Section: Gad65 Igg Antibodies and Gad65-specific T Cells In Spsmentioning

confidence: 94%

“…IgG from sera of patients with GAD65 IgG antibody-associated SPS induced neurophysiological and biochemical SPS-correlates in rats (Manto 2007). This phenomenon was not observed after administration of IgG antibodies from T1D patients, which indicate that SPS could be the direct consequence of antibody-mediated neuronal dysfunction (Manto 2007).…”

Section: Gad65 Igg Antibodies and Gad65-specific T Cells In Spsmentioning

confidence: 99%

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MS and clinically isolated syndromes: Shared specificity but diverging clonal patterns of virus‐specific IgG antibodies produced in vivo and by CSF B cells in vitro

Skorstad

Vandvik

Vartdal

et al. 2009

Euro J of Neurology

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Background: Intrathecal synthesis of oligoclonal IgG antibodies against measles virus (MeV), varicella zoster virus (VZV) and herpes simplex virus type‐1 (HSV‐1) is a characteristic feature multiple sclerosis (MS). Methods: We have used isoelectric focusing‐immunoblot to define the clonal patterns of IgG and of IgG antibodies to MeV, VZV and HSV‐1 in supernatants of in vitro cultures of peripheral blood lymphocytes (PBL) and cerebrospinal fluid (CSF) cells and in sera and CSF from three patients with MS and three patients with clinically isolated syndromes (CIS) suspective of demyelinating disease. Results: In vitro synthesis of IgG by PBL was not detected in any patient. In contrast, in vitro synthesis by CSF cells of oligoclonal IgG and oligoclonal IgG antibodies to one or two of the three viruses tested was observed in all six patients. The clonal patterns of the in vitro synthesized IgG and virus specific IgG differed to varying extent from those synthesized intrathecally in vivo. However, in each patient, the in vitro and in vivo intrathecally produced antibodies displayed specificity for the same viruses. The addition of B cell activating factor (BAFF) had no effect on the amounts or clonal patterns of either total IgG or virus‐specific IgG produced by CSF cells in vitro. Conclusion: Virus specific B cells capable of spontaneous IgG synthesis are clonally expanded in the CSF of patients with MS. The B‐cell repertoire in CSF samples is only partially representative of the intrathecal B‐cell repertoire.

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Section: Gad65 Igg Antibodies and Gad65-specific T Cells In Spsmentioning

confidence: 94%

Section: Gad65 Igg Antibodies and Gad65-specific T Cells In Spsmentioning

confidence: 99%

MS and clinically isolated syndromes: Shared specificity but diverging clonal patterns of virus‐specific IgG antibodies produced in vivo and by CSF B cells in vitro

Skorstad

Vandvik

Vartdal

et al. 2009

Euro J of Neurology

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“…This overlap emphasizes a possible common mechanism, which is probably related to the widespread distribution of GAD throughout the CNS 1,2,4,6 . A personal or familial history of other autoimmune diseases such as autoimmune diabetes mellitus, Addison's disease, hemolytic anemia or thyroiditis is commonly found in CA-GAD-ab 6,22 .…”

mentioning

confidence: 91%

“…It is found primarily in GABAergic neurons and in beta cells in the islets of Langerhans in the pancreas 2,4 . Glutamic acid decarboxylase is produced in two different isoforms with molecular weights of 65 and 67 kilodaltons (GAD65 and GAD67) encoded by two distinct genes; the main target for GAD-ab in neurological diseases is GAD65 1,2,3,4 . The cerebellum is an encephalic region highly susceptible to immune-mediated mechanisms.…”

mentioning

confidence: 99%

“…It should be emphasized, however, that even if there is no association with endocrinopathy, all patients with new onset of unexplained cerebellar ataxia should be investigated for treatable conditions 6 such as CA-GAD-ab. Cerebrospinal fluid analysis may be normal or may show oligoclonal bands, mild pleocytosis and intrathecal synthesis of GAD-abs 1,2,3 . Brain MRI may also be normal or may reveal cerebellar atrophy 1,2,3,5 .…”

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confidence: 99%

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Clinical characteristics of patients with cerebellar ataxia associated with anti-GAD antibodies

Aguiar

Fragoso

Albuquerque

et al. 2017

Arq. Neuro-Psiquiatr.

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The enzyme glutamic acid decarboxylase (GAD), present in GABAergic neurons and in pancreatic beta cells, catalyzes the conversion of gamma-aminobutyric acid (GABA). The cerebellum is highly susceptible to immune-mediated mechanisms, with the potentially treatable autoimmune cerebellar ataxia associated with the GAD antibody (CA-GAD-ab) being a rare, albeit increasingly detected condition. Few cases of CA-GAD-ab have been described. Methods This retrospective and descriptive study evaluated the clinical characteristics and outcomes of patients with CA-GAD-ab. Result Three patients with cerebellar ataxia, high GAD-ab titers and autoimmune endocrine disease were identified. Patients 1 and 2 had classic stiff person syndrome and insidious-onset cerebellar ataxia, while Patient 3 had pure cerebellar ataxia with subacute onset. Patients received intravenous immunoglobulin therapy with no response in Patients 1 and 3 and partial recovery in Patient 2. Conclusion CA-GAD-ab is rare and its clinical presentation may hamper diagnosis. Clinicians should be able to recognize this potentially treatable autoimmune cerebellar ataxia.

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Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase

Hadjivassiliou

Aeschlimann

Strigun

et al. 2008

Annals of Neurology

238

175

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Effects of anti–glutamic acid decarboxylase antibodies associated with neurological diseases

Cited by 235 publications

References 37 publications

MS and clinically isolated syndromes: Shared specificity but diverging clonal patterns of virus‐specific IgG antibodies produced in vivo and by CSF B cells in vitro

MS and clinically isolated syndromes: Shared specificity but diverging clonal patterns of virus‐specific IgG antibodies produced in vivo and by CSF B cells in vitro

Clinical characteristics of patients with cerebellar ataxia associated with anti-GAD antibodies

Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase

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