title: TACE mRNA expression in peripheral mononudear cells precedes new lesions on MRI in multiple sclerosis.
abstract: Tumor necrosis factor-alpha (TNF-alpha) is involved in the pathogenesis of multiple sclerosis (MS). It has to be released from its cell membrane-bound precursor by proteolytic cleavage. This is mainly performed by a member of the ADAM (a disintegrin and metalloproteinase) family of enzymes, TNF-alpha-converting enzyme (TACE, ADAM 17). In a longitudinal study on 11 relapsing-remitting MS patients, we qualitatively determined mRNA expression of TNF-alpha and TACE in peripheral blood mononuclear cells (PBMCs) without ex vivo stimulation. mRNA expression was related to disease activity as assessed by monthly gadolinium (Gd)-enhanced brain magnetic resonance imaging (MRI). Patients found positive for TACE mRNA in PBMCs showed a significantly higher mean number of new Gd-enhancing lesions per scan one month following PBMC sampling.
authors.affiliation: Department of Neurology, Karl Franzens University, Auenbruggerplatz 22, Graz A-8036, Austria. thomas.seifert@kfunigraz.ac.at
authors.forename: T
authors.initials: T
authors.lastname: Seifert
authors.forename: B C
authors.initials: BC
authors.lastname: Kieseier
authors.forename: S
authors.initials: S
authors.lastname: Ropele
authors.forename: S
authors.initials: S
authors.lastname: Strasser-Fuchs
authors.forename: F
authors.initials: F
authors.lastname: Quehenberger
authors.forename: F
authors.initials: F
authors.lastname: Fazekas
authors.forename: H P
authors.initials: HP
authors.lastname: Hartung
mesh_terms: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000328:Adult; D001812:Blood-Brain Barrier / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000473:pathology; D004790:Enzyme Induction / Q000276:immunology; D005260:Female; D005682:Gadolinium; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005682:Gadolinium; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human