title: Survivin as a potential mediator to support autoreactive cell survival in myasthenia gravis: a human and animal model study.
abstract: The mechanisms that underlie the development and maintenance of autoimmunity in myasthenia gravis are poorly understood. In this investigation, we evaluate the role of survivin, a member of the inhibitor of apoptosis protein family, in humans and in two animal models. We identified survivin expression in cells with B lymphocyte and plasma cells markers, and in the thymuses of patients with myasthenia gravis. A portion of survivin-expressing cells specifically bound a peptide derived from the alpha subunit of acetylcholine receptor indicating that they recognize the peptide. Thymuses of patients with myasthenia gravis had large numbers of survivin-positive cells with fewer cells in the thymuses of corticosteroid-treated patients. Application of a survivin vaccination strategy in mouse and rat models of myasthenia gravis demonstrated improved motor assessment, a reduction in acetylcholine receptor specific autoantibodies, and a retention of acetylcholine receptor at the neuromuscular junction, associated with marked reduction of survivin-expressing circulating CD20+ cells. These data strongly suggest that survivin expression in cells with lymphocyte and plasma cell markers occurs in patients with myasthenia gravis and in two animal models of myasthenia gravis. Survivin expression may be part of a mechanism that inhibits the apoptosis of autoreactive B cells in myasthenia gravis and other autoimmune disorders.
authors: Department of Pharmacology and Physiology, George Washington University, Washington, District of Columbia, United States of America.
authors: Linda L
authors: LL
authors: Kusner
authors: Department of Neurosurgery, Roswell Park Cancer Institute, Buffalo, New York, United States of America; Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors: Michael J
authors: MJ
authors: Ciesielski
authors: Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.
authors: Alexander
authors: A
authors: Marx
authors: Department of Neurology, George Washington University, Washington, District of Columbia, United States of America.
authors: Henry J
authors: HJ
authors: Kaminski
authors: Department of Neurosurgery, Roswell Park Cancer Institute, Buffalo, New York, United States of America; Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors: Robert A
authors: RA
authors: Fenstermaker
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002470:Cell Survival; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology / Q000378:metabolism; D000077022:Survivin; D013950:Thymus Gland / Q000378:metabolism; D055815:Young Adult
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D011950:Receptors, Cholinergic; D000077022:Survivin