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Antigen-specific apheresis of pathogenic autoantibodies from myasthenia gravis sera.

Abstract：

:Myasthenia gravis (MG) is usually caused by autoantibodies against muscle nicotinic acetylcholine receptor (AChR), which is composed of five subunits (alpha(2)betagammadelta or alpha(2)betaepsilondelta). Current treatments, including plasmapheresis, are nonspecific, causing several side effects. We aim to develop an antigen-specific alternative to plasmapheresis, since the latter removes indispensable plasma components in addition to anti-AChR antibodies. We are developing a method for the selective depletion of the anti-AChR autoantibodies from patients' plasma through the construction of "immunoadsorbent" columns carrying AChR domains. We have expressed the extracellular domains (ECDs, amino acids approximately 1-210/220) of all human muscle AChR subunits in Pichia pastoris and, in preliminary experiments, in E. coli. The ECDs were immobilized (individually or mixed) on Sepharose beads, producing Sepharose-ECD columns, which were tested for their immunoadsorbing capacity on MG sera and shown to specifically eliminate major autoantibody fractions from several MG sera. The immobilized ECDs remained stable and did not dissociate from their matrix after incubation with serum, whereas the procedure was neither toxic nor immunogenic in two experimental rabbits. Testing the intact or antibody-depleted MG sera and the affinity purified autoantibodies showed that both the intact sera and the purified autoantibodies, but not the antibody-depleted sera, could induce AChR loss in cell cultures and experimental MG in rats. This preliminary study suggests that the myasthenic potency of MG sera is entirely due to their anti-AChR antibodies and therefore their depletion should be of therapeutic value. We conclude that ECD-mediated immunoadsorption can be used as an efficient, antigen-specific therapy for MG.

journal_name

Ann N Y Acad Sci

journal_title

Annals of the New York Academy of Sciences

authors

Tzartos SJ,Bitzopoulou K,Gavra I,Kordas G,Jacobson L,Kostelidou K,Lagoumintzis G,Lazos O,Poulas K,Sideris S,Sotiriadis A,Trakas N,Zisimopoulou P

doi

10.1196/annals.1405.017

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

291-9

eissn

0077-8923

issn

1749-6632

pii

1132/1/291

journal_volume

1132

pub_type

杂志文章

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Antigen-specific apheresis of pathogenic autoantibodies from myasthenia gravis sera.