Specific immunoadsorption of the autoantibodies from myasthenic patients using the extracellular domain of the human muscle acetylcholine receptor alpha-subunit. Development of an antigen-specific therapeutic strategy.
Antibodies against the acetylcholine receptor (AChR) are the main pathogenic factor in myasthenia gravis (MG). Clinical improvement correlates well with a reduction in levels of circulating anti-AChR antibodies, and plasmapheresis is an efficient short-term MG treatment. The Sepharose-immobilized N-terminal extracellular domain of human muscle AChR alpha-subunit was used to immunoadsorb anti-AChR autoantibodies from 50 MG patients sera. The immunoadsorbents removed 60-94% of the anti-AChR antibodies in 10 sera and a mean of 35% from all samples combined. Immunoadsorption was fast, efficient, and the columns could be used repeatedly without any release or proteolysis of the polypeptide, suggesting the feasibility of antigen-specific MG immunoadsorption therapy.
Psaridi-Linardaki
Loukia
L
Department of Biochemistry, Hellenic Pasteur Institute, 127 Vas Sofias Ave., 11521 Athens, Greece.
Trakas
Nikos
N
Mamalaki
Avgi
A
Tzartos
Socrates J
SJ
D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000378:metabolism*; D001666:Binding Sites, Antibody; D000939:Epitopes / Q000276:immunology / Q000378:metabolism*; D017743:Equipment Reuse; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism; D007163:Immunosorbent Techniques; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism*; D009157:Myasthenia Gravis / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D010843:Pichia / Q000235:genetics; D010949:Plasma / Q000201:enzymology; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000276:immunology / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D010446:Peptide Fragments; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D010447:Peptide Hydrolases