Distinct time pattern of complement activation and cytotoxic T cell response in Guillain-Barré syndrome
Autor(es): Wanschitz Julia,Maier Hans,Lassmann Hans,Budka Herbert,Berger Thomas
Resumo: Humoural and cellular immune mechanisms are involved in the pathogenesis of Guillain-Barré syndrome (GBS). While activation of complement has been implicated in the initiation of myelin damage, we provide data here on the role of cellular cytotoxicity in GBS. Archival autopsy tissues including spinal roots, dorsal root ganglia and peripheral nerve were examined from 11 subjects who died 1 day to 8 weeks after onset of symptoms from GBS exhibiting a primary demyelinating pathology. In order to study the extent of humoural and cellular immune processes with regard to disease duration, a broad panel of antibodies to immunological and cellular markers was used to visualize the stage of demyelination, the deposition of complement components and expression of CD59, and to characterize cell infiltrates. Deposits of C9neo antigen on degenerating myelin sheaths were predominantly detected in acute cases. Expression of CD59 was upregulated on demyelinating fibres, but did not correlate with the presence of C9neo antigen or duration of disease. Quantitative analysis of endoneurial T cells showed a correlation between the density of CD3+ T cells per square unit and the degree of demyelination, but not with the duration of disease. The ratio of CD8+ to CD3+ T cells, however, was significantly increased in cases of GBS with a subacute course. Granzyme B positive lymphocytes and upregulation of MHC class I molecules on Schwann cells and myelin sheaths were detected in cases with more than 4 weeks disease duration. These findings implicate an important role of cytotoxic T cell responses for myelin damage in subacute stages of GBS.
Palavras-Chave: CD59; Cytotoxic T-cell response; C9neo antigen; Granzyme B; Guillain-Barré syndrome
Imprenta: Brain : A Journal of Neurology, v. 126, n. 9, p. 2034-2042, 2003
Identificador do objeto digital: 10.1093/brain/awg207
Descritores: Guillain-Barre Syndrome - Biosynthesis ; Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Cytopathology ; Guillain-Barre Syndrome - Immune response ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Antibodies ; Guillain-Barre Syndrome - Immunology
Data de publicação: 2003