title: Inhibition of acute passive transfer experimental autoimmune myasthenia gravis with Fab antibody to complement C6.
abstract: The role of the lytic complement C5b-9 membrane attack complex (MAC) in acute passive transfer experimental autoimmune myasthenia gravis (EAMG) produced in rats was investigated by in vivo inhibition of MAC formation with anti-C6 Fab. Anti-C6 Fab totally inhibited in vitro serum hemolytic activity, but did not consume or inhibit early complement pathways. Injection of rats with 0.12 mg/ml anti-C6 Fab reduced serum C6 to 8% and inhibited the muscle weakness, electrophysiologic abnormalities and loss of acetylcholine receptor (AChR) associated with acute EAMG. This level of C6 inhibition reduced the total serum complement hemolytic activity to 29% of normal but did not reduce the serum levels of complement components C3, C5, or C7. Treatment of rats with lower amounts of anti-C6 Fab (0.08 mg/ml) also inhibited clinical and electrophysiologic signs of EAMG, however, the lower amount of anti-C6 did not prevent the loss of muscle AChR. Both the higher and the lower amount of anti-C6 Fab inhibited the accumulation of macrophages at muscle motor end-plates. The inhibition by anti-C6 indicates that muscle weakness and electrophysiologic abnormalities associated with EAMG are dependent on the complement MAC, and that muscle weakness results from tissue injury in addition to loss of muscle membrane and AChR.
authors.affiliation: Department of Pathology and Laboratory Medicine, Hahnemann University, Philadelphia, PA 19102-1192.
authors.forename: G
authors.initials: G
authors.lastname: Biesecker
authors.forename: C M
authors.initials: CM
authors.lastname: Gomez
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D003182:Complement C5 / Q000032:analysis; D015936:Complement C5a; D003183:Complement C6 / Q000276:immunology*; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000502:physiology; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D008264:Macrophages / Q000473:pathology; D009157:Myasthenia Gravis / Q000276:immunology* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000032:analysis
chemical_list: D003182:Complement C5; D003183:Complement C6; D015938:Complement Membrane Attack Complex; D007140:Immunoglobulin Fab Fragments; D011950:Receptors, Cholinergic; D015936:Complement C5a; D003165:Complement System Proteins