Direct proof of the in vivo pathogenic role of the AChR autoantibodies from myasthenia gravis patients

• Published in: PloS one 2014-09, Vol.9 (9), p.e108327
• Main Authors: Kordas, Gregory, Lagoumintzis, George, Sideris, Sotirios, Poulas, Konstantinos, Tzartos, Socrates J
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors; Animals; Autoantibodies; Autoantibodies - blood; Autoimmune diseases; Biology and Life Sciences; Depletion; Humans; Immunization; Immunoglobulins; In vivo methods and tests; Kinases; Muscle, Skeletal - immunology; Muscles; Myasthenia; Myasthenia gravis; Myasthenia Gravis - immunology; Neuromuscular junctions; Patients; Pharmacy; Rats; Receptors, Cholinergic - immunology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0108327

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.