TACE mRNA expression in peripheral mononudear cells precedes new lesions on MRI in multiple sclerosis.
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.
Seifert
T
T
Department of Neurology, Karl Franzens University, Auenbruggerplatz 22, Graz A-8036, Austria. thomas.seifert@kfunigraz.ac.at
Kieseier
B C
BC
Ropele
S
S
Strasser-Fuchs
S
S
Quehenberger
F
F
Fazekas
F
F
Hartung
H P
HP
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
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005682:Gadolinium; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human