title: Distinct time pattern of complement activation and cytotoxic T cell response in Guillain-Barré syndrome.
abstract: 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.
authors.affiliation: Department of Neurology, University of Innsbruck, Anichstrasse 35, Innsbruck, A-6020 Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Wanschitz
authors.forename: Hans
authors.initials: H
authors.lastname: Maier
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Herbert
authors.initials: H
authors.lastname: Budka
authors.forename: Thomas
authors.initials: T
authors.lastname: Berger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018957:CD59 Antigens / Q000378:metabolism; D003167:Complement Activation / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D005727:Ganglia, Spinal / Q000473:pathology; D053804:Granzymes; D020275:Guillain-Barre Syndrome / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000378:metabolism; D013126:Spinal Nerve Roots / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D018957:CD59 Antigens; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases