title: Direct proof of the in vivo pathogenic role of the AChR autoantibodies from myasthenia gravis patients.
abstract: Several studies have suggested that the autoantibodies (autoAbs) against muscle acetylcholine receptor (AChR) of myasthenia gravis (MG) patients are the main pathogenic factor in MG; however, this belief has not yet been confirmed with direct observations. Although animals immunized with AChR or injected with anti-AChR monoclonal Abs, or with crude human MG Ig fractions exhibit MG symptoms, the pathogenic role of isolated anti-AChR autoAbs, and, more importantly, the absence of pathogenic factor(s) in the autoAb-depleted MG sera has not yet been shown by in vivo studies. Using recombinant extracellular domains of the human AChR α and β subunits, we have isolated autoAbs from the sera of four MG patients. The ability of these isolated anti-subunit Abs and of the Ab-depleted sera to passively transfer experimental autoimmune MG in Lewis rats was investigated. We found that the isolated anti-subunit Abs were at least as efficient as the corresponding whole sera or whole Ig in causing experimental MG. Abs to both α- and β-subunit were pathogenic although the anti-α-subunit were much more efficient than the anti-β-subunit ones. Interestingly, the autoAb-depleted sera were free of pathogenic activity. The later suggests that the myasthenogenic potency of the studied anti-AChR MG sera is totally due to their anti-AChR autoAbs, and therefore selective elimination of the anti-AChR autoAbs from MG patients may be an efficient therapy for MG.
authors.affiliation: Department of Pharmacy, University of Patras, Patras, Greece.
authors.forename: Gregory
authors.initials: G
authors.lastname: Kordas
authors.affiliation: Department of Pharmacy, University of Patras, Patras, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Lagoumintzis
authors.affiliation: Department of Pharmacy, University of Patras, Patras, Greece.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Sideris
authors.affiliation: Department of Pharmacy, University of Patras, Patras, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Poulas
authors.affiliation: Department of Pharmacy, University of Patras, Patras, Greece; Department of Biochemistry, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Socrates J
authors.initials: SJ
authors.lastname: Tzartos
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D006801:Humans; D018482:Muscle, Skeletal / Q000276:immunology*; D009157:Myasthenia Gravis / Q000276:immunology*; D051381:Rats; D011950:Receptors, Cholinergic / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D011950:Receptors, Cholinergic