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

J Neuroimmunol. 2005 Feb;159(1-2):183-91. doi: 10.1016/j.jneuroim.2004.10.002. Epub 2004 Nov 23.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Specificity
  • Autoantibodies / blood
  • Autoantibodies / metabolism*
  • Binding Sites, Antibody
  • Epitopes / immunology
  • Epitopes / metabolism*
  • Equipment Reuse
  • Extracellular Space / immunology
  • Extracellular Space / metabolism*
  • Humans
  • Hydrolysis
  • Immunoglobulin G / blood
  • Immunoglobulin G / metabolism
  • Immunosorbent Techniques
  • Muscle, Skeletal / immunology
  • Muscle, Skeletal / metabolism*
  • Myasthenia Gravis / blood
  • Myasthenia Gravis / immunology*
  • Myasthenia Gravis / therapy*
  • Peptide Fragments / biosynthesis
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Peptide Hydrolases / metabolism
  • Pichia / genetics
  • Plasma / enzymology
  • Protein Structure, Tertiary
  • Protein Subunits / immunology
  • Protein Subunits / metabolism*
  • Receptors, Nicotinic / immunology
  • Receptors, Nicotinic / metabolism*
  • Time Factors

Substances

  • Autoantibodies
  • Epitopes
  • Immunoglobulin G
  • Peptide Fragments
  • Protein Subunits
  • Receptors, Nicotinic
  • Peptide Hydrolases