Myasthenia gravis: further electrophysiological and ultrastructural analysis of transmission failure in the mouse passive transfer model.

Toyka, Klaus V.; Birnberger, Karl L.; Anzil, A. P.; Schlegel, Christiane; Besinger, U. A.; Strüppler, A.

doi:10.1136/jnnp.41.8.746

Cited by 27 publications

(2 citation statements)

References 34 publications

(55 reference statements)

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“…Harbs et a1 ( 5 ) have confirmed these results, and, by means of an antibody-dependent lymphocyte-mediated cytotoxicity (ADLC) reaction, have demonstrated the antibody-like character of a majority of MW-IgM against peripheral myelin. A humoral immune mechanism of IgG myeloma neuropathy has been made probable by passive transfer to mice (2), analogous to earlier studies in myasthenia gravis (15,16). Following these transfer models, we have injected monoclonal IgM of MW patients sera intraperitoneally (i.p.)…”

mentioning

confidence: 75%

Polyneuropathy in Waldenström s macroglobulinaemia. Passive transfer from man to mouse

Hoppe

Dräger

Patzold

et al. 1987

Acta Neurologica Scandinavica

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To support the hypothesis of an immunopathogenesis of polyneuropathy in Waldenström's macroglobulinaemia (MW), serum IgM fractions of MW patients were applied intraperitoneally to mice for 17 days. Sections of liver, kidney, M. glutaeus maximus, central nervous system (CNS) and both Nn. ischiadici were examined for IgM, IgG, C3 and as control IgD with PAP-immunostaining. IgM deposits were found in every organ except the CNS. In peripheral nerves larger amounts were visualized in perineurium and endoneural space, whereas myelin lamellae and periaxon did not stain. Therefore, perhaps our investigation reveals a greater permeability of the blood-nerve barrier (BNB) compared with the blood-brain barrier (BBB). The involvement of the monoclonal IgM of MW, which has been shown to react in vitro with peripheral nerve constituents, appears possible in the pathogenesis of polyneuropathy.

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mentioning

confidence: 75%

Polyneuropathy in Waldenström s macroglobulinaemia. Passive transfer from man to mouse

Hoppe

Dräger

Patzold

et al. 1987

Acta Neurologica Scandinavica

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“…The relative contribution of non-complement-mediated mechanisms to human MG is poorly defined. Administration into mice of even large quantities of human autoantibodies (equal to 50% of the total mouse circulating mouse IgG) produces only mild weakness (7,24). Because human complement is not co-administered, weakness would likely only develop from antigenic modulation or impairment of AChR function.…”

Section: Evidence Of Complement As An Effector Mechanism In Myasthenimentioning

confidence: 99%

Complement Inhibitor Therapy for Myasthenia Gravis

2020

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Complement activation as a driver of pathology in myasthenia gravis (MG) has been appreciated for decades. The terminal complement component [membrane attack complex (MAC)] is found at the neuromuscular junctions of patients with MG. Animals with experimental autoimmune MG are dependent predominantly on an active complement system to develop weakness. Mice deficient in intrinsic complement regulatory proteins demonstrate a significant increase in the destruction of the neuromuscular junction. As subtypes of MG have been better defined, it has been appreciated that acetylcholine receptor antibody-positive disease is driven by complement activation. Preclinical assessments have confirmed that complement inhibition would be a viable therapeutic approach. Eculizumab, an antibody directed toward the C5 component of complement, was demonstrated to be effective in a Phase 3 trial with subsequent approval by the Federal Drug Administration of the United States and other worldwide regulatory agencies for its use in acetylcholine receptor antibodypositive MG. Second-and third-generation complement inhibitors are in development and approaching pivotal efficacy evaluations. This review will summarize the history and present the state of knowledge of this new therapeutic modality.

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