Myasthenia gravis: An autoimmune response against the acetylcholine receptor

Graus, Y.; Baets, Marc H. De

doi:10.1007/bf02918370

Cited by 33 publications

(14 citation statements)

References 249 publications

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“…In contrast to the long lasted opinion that autoantibodies are auto-aggressive like in Myasthenia gravis [22,23], previous studies could also show the protective potential of autoantibodies. In Alzheimers' disease autoantibodies against Aβ, which are also found downregulated in the patients, convey a protective effect by inhibiting oligomerization of Aβ peptides [24,25].…”

Section: Discussionmentioning

confidence: 64%

GFAP antibodies show protective effect on oxidatively stressed neuroretinal cells via interaction with ERP57

Wilding

Bell

Funke

et al. 2015

Journal of Pharmacological Sciences

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The pathogenesis of glaucoma, a common neurodegenerative disease, involves an immunologic component. Changes in the natural autoantibody profile of glaucoma patients were detected, showing not only up-regulated but also down-regulated immunoreactivities. In recent studies we were able to demonstrate that the antibody changes have a large influence on protein profiles of neuroretinal cells. Furthermore we could demonstrate neuroprotective potential of one of the down-regulated antibodies (γ-synuclein antibody). Anti-GFAP antibody is another antibody found down-regulated in glaucoma patients. Since GFAP expression is intensified in glaucomatous retina, the aim of this study was to detect the effect of GFAP antibodies on neuroretinal cells. This is realized with a viability-test as well as proteomic analysis of cells incubated with GFAP antibodies. Furthermore, possible interaction partners of the GFAP antibody in neuroretinal cells were identified by western blot, mass spectrometry and indirect immunofluorescence staining. We found that the GFAP antibody is able to protect cells from oxidative stress, which is due to changed protein expressions of the actin cytoskeleton. Furthermore we detected a cross-reaction of the antibody to endoplasmic reticulum resident protein 57 on the cell membrane, which seems to lead to a changed signaling in the cells triggering the protective effects.

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Section: Discussionmentioning

confidence: 64%

GFAP antibodies show protective effect on oxidatively stressed neuroretinal cells via interaction with ERP57

Wilding

Bell

Funke

et al. 2015

Journal of Pharmacological Sciences

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“…Known examples include antiacetylcholine receptor antibodies in myasthenia gravis [26], anti-calcium channel antibodies in EatonLambert syndrome [27,28], amyotrophic lateral sclerosis [27][28][29][30] and anti-myelin basic protein autoreactive lymphocytes in multiple sclerosis [31,32].…”

Section: Discussionmentioning

confidence: 99%

Autoimmunity to the Glutamate Receptor in Mice— A Model for Rasmussen's Encephalitis?

Levite

Hermelin

1999

Journal of Autoimmunity

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“…Yet in many of these models, the Ag that is implicated in the human autoimmune disorder has not been used, often because the diseasecausing Ag had not been identified (1). Thus, we have chosen to focus on myasthenia gravis (MG), 5 one of the few autoimmune disorders in which the self-Ag has been clearly delineated. MG is mediated by Abs against the patient's acetylcholine receptors (AChR; primarily the ␣-chain) at the neuromuscular junction (2).…”

mentioning

confidence: 99%

“…In both humans and in mouse models, there is a MHC-linked genetic susceptibility, suggesting a T cell regulatory function (3,4). In addition, the occurrence of thymomas and thymic hyperplasias in many patients suggests a T cell association with disease (5). Interestingly, an immunodominant T cell response to certain AChR ␣-chain epitopes has been observed in MG animal models (6,7), and T cells from peripheral blood of MG patients react with predominant synthetic peptides of the AChR ␣-chain (5,8,9).…”

mentioning

confidence: 99%

“…In addition, the occurrence of thymomas and thymic hyperplasias in many patients suggests a T cell association with disease (5). Interestingly, an immunodominant T cell response to certain AChR ␣-chain epitopes has been observed in MG animal models (6,7), and T cells from peripheral blood of MG patients react with predominant synthetic peptides of the AChR ␣-chain (5,8,9). However, only a few T cell clones reacting to endogenously processed peptides of the intact AChR ␣-chain have been isolated from MG patients (10 -12).…”

mentioning

confidence: 99%

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Split Tolerance in a Novel Transgenic Model of Autoimmune Myasthenia Gravis

Stacy¹,

Gelb²,

Koop³

et al. 2002

The Journal of Immunology

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Because it is one of the few autoimmune disorders in which the target autoantigen has been definitively identified, myasthenia gravis (MG) provides a unique opportunity for testing basic concepts of immune tolerance. In most MG patients, Abs against the acetylcholine receptors (AChR) at the neuromuscular junction can be readily identified and have been directly shown to cause muscle weakness. T cells have also been implicated and appear to play a role in regulating the pathogenic B cells. A murine MG model, generated by immunizing mice with heterologous AChR from the electric fish Torpedo californica, has been used extensively. In these animals, Abs cross-react with murine AChR; however, the T cells do not. Thus, to study tolerance to AChR, a transgenic mouse model was generated in which the immunodominant Torpedo AChR (T-AChR) α subunit is expressed in appropriate tissues. Upon immunization, these mice showed greatly reduced T cell responses to T-AChR and the immunodominant α-chain peptide. Limiting dilution assays suggest the likely mechanism of tolerance is deletion or anergy. Despite this tolerance, immunization with intact T-AChR induced anti-AChR Abs, including Abs against the α subunit, and the incidence of MG-like symptoms was similar to that of wild-type animals. Furthermore, evidence suggests that this B cell response to the α-chain receives help from T cells directed against the other AChR polypeptides (β, γ, or δ). This model offers a novel opportunity to elucidate mechanisms of tolerance regulation to muscle AChR and to clarify the role of T cells in MG.

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Myasthenia gravis: An autoimmune response against the acetylcholine receptor

Cited by 33 publications

References 249 publications

GFAP antibodies show protective effect on oxidatively stressed neuroretinal cells via interaction with ERP57

GFAP antibodies show protective effect on oxidatively stressed neuroretinal cells via interaction with ERP57

Autoimmunity to the Glutamate Receptor in Mice— A Model for Rasmussen's Encephalitis?

Split Tolerance in a Novel Transgenic Model of Autoimmune Myasthenia Gravis

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