Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
3065490 | Journal of Neuroimmunology | 2007 | 7 Pages |
The muscle nicotinic acetylcholine receptor (nAChR) is the major autoantigen in the autoimmune disease myasthenia gravis (MG), in which autoantibodies bind to, and cause loss of, nAChRs. Antibody-mediated nAChR loss is caused by the action of complement and by the acceleration of nAChR internalization caused by antibody-induced cross-linking of nAChR molecules (antigenic modulation). To obtain an insight into the role of the various anti-nAChR antibody specificities in MG, we have studied nAChR antigenic modulation caused by isolated anti-subunit autoantibodies. Autoantibodies against the nAChR α or β subunits were isolated from four MG sera by affinity chromatography on columns carrying immobilized recombinant extracellular domains of human nAChR expressed in the yeast Pichia pastoris. The isolated anti-α and anti-β autoantibodies, as well as untreated MG sera, induced nAChR antigenic modulation in TE671 cells. Partially antibody-depleted sera exhibited reduced modulating activity, whereas a serum completely depleted of anti-nAChR antibodies exhibited no nAChR modulation. Interestingly, the anti-α autoantibodies were, on average, ∼ 4.3 times more effective than the anti-β autoantibodies. The present work supports the notion that anti-nAChR autoantibodies may be the sole nAChR-reducing factor in anti-nAChR antibody-seropositive MG, and that anti-α-subunit autoantibodies are the dominant pathogenic autoantibody specificity.