title: Upregulated survivin expression in activated T lymphocytes correlates with disease activity in multiple sclerosis.
abstract: Programmed cell death (apoptosis) is critical for the normal development and homeostasis of the immune system. There is emerging evidence that failure of apoptosis to eliminate potentially pathogenic, autoreactive T lymphocytes may be involved in the pathogenesis of multiple sclerosis (MS). This failure is related to multiple abnormalities of apoptosis-regulatory molecules that involve survivin, a recently described cell cycle-regulated anti-apoptosis protein. In this study, we investigated the relationship between survivin expression in peripheral T lymphocytes and clinical features of MS. We detected a significant over-expression of survivin in mitogen stimulated T lymphocytes from patients with active MS when compared with corresponding expression in patients with stable MS or those with inflammatory and non-inflammatory neurologic disorders. This over-expression of survivin in patients with active MS correlated with cellular resistance to apoptosis and with features of disease activity, such as disease duration and the number of enhanced lesions on cranial magnetic resonance imaging. There was no correlation between cellular survivin levels and the expression of other apoptosis-inhibitory proteins, such as Bcl-2 and Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein (FLIP). Our findings indicate that cellular over-expression of the novel anti-apoptosis protein survivin is a feature of clinically active MS.
authors.affiliation: Department of Neuroimmunology, Guy's, King's and St Thomas' School of Medicine, Guy's Hospital, London, UK. m.k.sharief@kcl.ac.uk
authors.forename: M K
authors.initials: MK
authors.lastname: Sharief
authors.forename: M A
authors.initials: MA
authors.lastname: Noori
authors.forename: M R
authors.initials: MR
authors.lastname: Douglas
authors.forename: Y K
authors.initials: YK
authors.lastname: Semra
mesh_terms: D017668:Age of Onset; D017209:Apoptosis / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000276:immunology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008279:Magnetic Resonance Imaging; D008869:Microtubule-Associated Proteins / Q000276:immunology*; D008934:Mitogens; D009103:Multiple Sclerosis / Q000276:immunology* / Q000503:physiopathology; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D000077022:Survivin; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
chemical_list: C107489:BIRC5 protein, human; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D008934:Mitogens; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D019014:fas Receptor