TY - JOUR
T1 - Demyelination in primate autoimmune encephalomyelitis and acute multiple sclerosis lesions
T2 - A case for antigen-specific antibody mediation
AU - Raine, Cedric S.
AU - Cannella, Barbara
AU - Hauser, Stephen L.
AU - Genain, Claude P.
PY - 1999
Y1 - 1999
N2 - Neuropathological and ultrastructural features of central nervous system demyelination were compared in marmoset experimental autoimmune encephalomyelitis (EAE) induced with myelin/oligodendrocyte glycoprotein (MEG), and in 3 cases of multiple sclerosis (MS) displaying recent lesions. At the edges of EAE and MS lesions, a zone of myelin vacuolation was common, whereas in the lesion proper, myelin sheaths were consistently transformed into vesiculated membranous networks. These networks became dissociated from axons by cell processes from macrophages. Oligodendrocytes were remarkably spared and evidence of myelin repair was present but not prominent. Axonal pathology was more common in the MS material than in marmoset EAE. Immunocytochemistry, using gold-labeled encephalitogenic peptides of MeG and silver enhancement to detect MeG autoantibodies, revealed the presence of MOG-specific autoantibodies over vesiculated myelin networks. Gold-labeled antibody to IgG also gave a positive reaction. Gold-labeled peptide of myelin basic protein did not react with MOG/EAE tissue, but the same conjugate gave positive staining in MS (and in marmoset EAE induced by whole white matter), perhaps indicating broader spectrum immunoreactivity or sensitization to myelin antigens. Thus, vesicular disruption of myelin was a constant feature in these evolving, highly active lesions in primate EAE and MS and appeared causally related to the deposition of antigen-specific autoantibodies.
AB - Neuropathological and ultrastructural features of central nervous system demyelination were compared in marmoset experimental autoimmune encephalomyelitis (EAE) induced with myelin/oligodendrocyte glycoprotein (MEG), and in 3 cases of multiple sclerosis (MS) displaying recent lesions. At the edges of EAE and MS lesions, a zone of myelin vacuolation was common, whereas in the lesion proper, myelin sheaths were consistently transformed into vesiculated membranous networks. These networks became dissociated from axons by cell processes from macrophages. Oligodendrocytes were remarkably spared and evidence of myelin repair was present but not prominent. Axonal pathology was more common in the MS material than in marmoset EAE. Immunocytochemistry, using gold-labeled encephalitogenic peptides of MeG and silver enhancement to detect MeG autoantibodies, revealed the presence of MOG-specific autoantibodies over vesiculated myelin networks. Gold-labeled antibody to IgG also gave a positive reaction. Gold-labeled peptide of myelin basic protein did not react with MOG/EAE tissue, but the same conjugate gave positive staining in MS (and in marmoset EAE induced by whole white matter), perhaps indicating broader spectrum immunoreactivity or sensitization to myelin antigens. Thus, vesicular disruption of myelin was a constant feature in these evolving, highly active lesions in primate EAE and MS and appeared causally related to the deposition of antigen-specific autoantibodies.
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U2 - 10.1002/1531-8249(199908)46:2<144::AID-ANA3>3.0.CO;2-K
DO - 10.1002/1531-8249(199908)46:2<144::AID-ANA3>3.0.CO;2-K
M3 - Article
C2 - 10443879
AN - SCOPUS:0032839687
SN - 0364-5134
VL - 46
SP - 144
EP - 160
JO - Annals of Neurology
JF - Annals of Neurology
IS - 2
ER -