A new paraclinical CSF marker for hypoxia-like tissue damage in multiple sclerosis lesions.
Recent studies on the immunopathology of multiple sclerosis revealed a heterogeneity in the patterns of demyelination, suggesting interindividual differences in the mechanism responsible for myelin destruction. One of these patterns of demyelination, characterized by oligodendrocyte dystrophy and apoptosis, closely mimics myelin destruction in acute white matter ischaemia. In the course of a systematic screening for virus antigen expression in multiple sclerosis brains, we identified a monoclonal antibody against canine distemper virus, which detects a cross-reactive endogenous brain epitope, highly expressed in this specific subtype of actively demyelinating multiple sclerosis lesions with little or no immunoreactivity in other active multiple sclerosis cases. The respective epitope, which is a phosphorylation-dependent sequence of one or more proteins of 50, 70 and 115 kDa, is also expressed in a subset of active lesions of different virus-induced inflammatory brain diseases, but is present most prominently and consistently in acute lesions of white matter ischaemia. Its presence is significantly associated with nuclear expression of hypoxia-inducible factor-1 alpha within the lesions of both inflammatory and ischaemic brain diseases. The respective epitope is liberated into the CSF and, thus, may become a useful diagnostic tool to identify clinically a defined multiple sclerosis subtype.
Lassmann
Hans
H
Division of Neuroimmunology, Brain Research Institute, University of Vienna, Austria. hans.lassmann@univie.ac.at
Reindl
Markus
M
Rauschka
Helmut
H
Berger
Johannes
J
Aboul-Enein
Fahmy
F
Berger
Thomas
T
Zurbriggen
Andreas
A
Lutterotti
Andreas
A
Brück
Wolfgang
W
Weber
Jörg R
JR
Ullrich
Robert
R
Schmidbauer
Manfred
M
Jellinger
Kurt
K
Vandevelde
Marc
M
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002545:Brain Ischemia / Q000134:cerebrospinal fluid; D004216:Distemper / Q000150:complications; D004217:Distemper Virus, Canine / Q000276:immunology; D018792:Encephalitis, Viral / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D002534:Hypoxia, Brain / Q000175:diagnosis* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications* / Q000821:virology; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D015415:Biomarkers; D000939:Epitopes; D009419:Nerve Tissue Proteins