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Indexed by:期刊论文

Date of Publication:2011-09-01

Journal:JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A

Included Journals:Scopus、SCIE、EI、PubMed

Volume:98A

Issue:4

Page Number:589-595

ISSN No.:1549-3296

Key Words:myasthenia gravis; blood purification; 4-mercaptoethylpyridine; autoantibody; cytokine

Abstract:The role of immunoadsorption therapy is well established in the management of myasthenia gravis (MG), an autoimmune disorder characterized by muscle weakness and caused by circulating IgG antibodies with specificity against the acetylcholine receptor. Conventional immunoadsorbents that employ recombinant protein A as immobilized ligand suffer from the drawbacks of high cost and low stability. The objective of this work is to assess the safety and efficacy of a synthetic adsorbent for treating MG. Adsorption columns were prepared from a Sepharose-based adsorbent coupled to 4-mercaptoethylpyridine (MEP), which acted as immobilized ligands. Animal model of experimental autoimmune MG (EAMG) using Lewis rats was developed and treated by whole blood perfusion. The results showed that the treatments provided a significant amelioration of clinical weakness for EAMG rats, with clinic score decreasing from 2.08 +/- 0.38 to 1.25 +/- 0.27. After a treatment session of about 1.5 h, blood cell counts were not significantly changed. Serum levels of total IgG and acetylcholine receptor antibody were reduced by 37.1 +/- 6.5% and 35.6 +/- 8.6%, respectively. In addition, reduction in complement components C3 (47.1 +/- 6.7%), C4 (34.3 +/- 3.4%), inflammatory cytokines interleukin17 (10.4 +/- 2.7%), and tumor necrosis factor-alpha (8.2 +/- 3.1%) were also observed. This study demonstrated that MEP-based adsorbent not only removed pathogenic autoantibodies directly from the blood as with protein A adsorbents but also modulated cellular immunity through removal of complement components and related proinflammatory cytokines, thereby providing a potentially superior strategy for the treatment of MG. (C) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 98A: 589-595, 2011.