Pathogenesis of hyperacute experimental autoimmune myasthenia gravis: Acetylcholine receptor/cholinergic site/receptor function/autoimmunity

Mirta Mihovilovic, Diana Donnelly-Roberts, David P Richman, Marino Martinez-Carrion

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Three mAbs, mAbs 249E, 370, and 383C, directed against the α- bungarotoxin (αBgTx) binding site of the acetylcholine receptor (AChR) induce a hyperacute form of experimental autoimmune myasthenia gravis (EAMG), characterized by death within hours of mAb injection. To analyze the mechanisms of this effect, purified AChR-mAb complexes were investigated for their ability to bind the cholinergic agonist carbamylcholine and to undergo agonist-induced activation of the cholinergic ionophore. The three mAbs inhibited carbamylcholine binding, and, conversely, their binding to AChR was inhibited by carbamylcholine. All three completely inhibited carbamylcholine- induced T1+ influxes to AChR-rich vesicles. These data indicate that the severe hyperacute EAMG induced by these mAbs results from blockage of AChR function and that the role of such potent Abs (even if present in small amounts) in the pathogenesis of human myasthenia gravis deserves further investigation.

Original languageEnglish (US)
Pages (from-to)5997-6002
Number of pages6
JournalJournal of Immunology
Volume152
Issue number12
StatePublished - Jun 15 1994

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Autoimmune Experimental Myasthenia Gravis
Cholinergic Receptors
Autoimmunity
Carbachol
Bungarotoxins
Cholinergic Agonists
Myasthenia Gravis
Ionophores
Cholinergic Agents
Binding Sites
Injections

ASJC Scopus subject areas

  • Immunology

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Pathogenesis of hyperacute experimental autoimmune myasthenia gravis : Acetylcholine receptor/cholinergic site/receptor function/autoimmunity. / Mihovilovic, Mirta; Donnelly-Roberts, Diana; Richman, David P; Martinez-Carrion, Marino.

In: Journal of Immunology, Vol. 152, No. 12, 15.06.1994, p. 5997-6002.

Research output: Contribution to journalArticle

Mihovilovic, Mirta ; Donnelly-Roberts, Diana ; Richman, David P ; Martinez-Carrion, Marino. / Pathogenesis of hyperacute experimental autoimmune myasthenia gravis : Acetylcholine receptor/cholinergic site/receptor function/autoimmunity. In: Journal of Immunology. 1994 ; Vol. 152, No. 12. pp. 5997-6002.
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