In-line affinity chromatographic removal of specific antibody from rabbits with experimental myasthenia gravis as a prelude to immunotherapy.
Myasthenia gravis is an autoimmune disease in which antibodies are produced against one's acetylcholine receptors, resulting in complement-mediated membrane destruction and internalization of antibody-receptor complexes. Symptoms range from weakening of extraocular muscles to severe impairment of movement and breathing. Prior to administering a therapeutic agent to eliminate antibody-producing lymphocytes, it will be necessary to remove specific antibody from the circulation. This process was investigated in an animal model of ex vivo specific immunoadsorption using awake, conscious rabbits. Following arterial blood separation, plasma was pumped upward through an affinity column containing covalently-bound acetylcholine receptor. Treated plasma was returned to the rabbit. Within a one-hour ex vivo procedure, specific antibody levels could be lowered from 16.2 ng/ml to less than 0.6 ng/ml, a reduction of more than 95%. By washing the column, at least four exchanges could be performed before specific antibody removal significantly diminished. The effects of specific antibody removal upon muscle function varied among individual rabbits, but if symptoms were not severe following passive transfer of purified monoclonal antibody to induce myasthenia, removal of 60% of the total specific antibody resulted in clinical improvement, as monitored by an animal's response to gallamine triethiodide.
Hinman
C L
CL
Department of Medicinal & Biological Chemistry, University of Toledo, Ohio 43606, USA.
Stevens-Truss
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000915:Antibody Affinity; D001323:Autoantibodies / Q000097:blood*; D002846:Chromatography, Affinity / Q000379:methods*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007116:Immunization, Passive; D007167:Immunotherapy / Q000379:methods*; D009157:Myasthenia Gravis / Q000276:immunology / Q000628:therapy*; D010951:Plasma Exchange; D011817:Rabbits; D011863:Radioimmunoassay; D011950:Receptors, Cholinergic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D011950:Receptors, Cholinergic