Brain, Vol 120, Issue 8 1461-1483, Copyright © 1997 by Oxford University Press
FW Gay, TJ Drye, GW Dick and MM Esiri
Tissues from 13 exceptionally early cases of multiple sclerosis were
studied to identify and characterize the primary demyelinating lesion,
using a variety of histological and immunocytochemical methods.
Multifactorial cluster analysis identified five significantly distinct
lesion groups, which showed histological progression from simple microglial
lesions, predominating in tissues from the earliest cases, to complex
hypercellular fully demyelinated plaques, chiefly associated with cases of
intermediate duration. Quiescent lesions showing evidence of remyelination
were found at all stages of the disease studied, but hypocellular inactive
plaques, were associated with older cases. Evidence is presented that
initial demyelination is effected by activated resident microglia.
Undegraded myelin is initially enveloped by membranes bearing fixed
complexes of immunoglobulin and complement. In contrast with perivenous
encephalomyelitis, in which demyelination was dominated by T-cell
infiltration, multiple sclerosis lesions of comparable duration and
maturity exhibited humoral immune reactions. Parenchymal CD4+ T-cell
infiltration developed in association with subsequent plaque maturation.
These results emphasize the need for lesion staging when multiple sclerosis
tissues are being used in the investigation of pathogenic mechanisms, and
suggest that further analysis of the oligoclonal B-cell response may be
productive in the search for primary provoking antigens.
ARTICLES
The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. Identification and characterization of the primary demyelinating lesion
Department of Biomedical Science, Anglia Polytechnic University, Cambridge, UK.
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