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Astrocytes are a specific immunological target in Rasmussen's encephalitis
Author(s) -
Bauer Jan,
Elger Christian E.,
Hans Volkmar H.,
Schramm Johannes,
Urbach Horst,
Lassmann Hans,
Bien Christian G.
Publication year - 2007
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21148
Subject(s) - astrocyte , microglia , biology , pathology , granzyme b , cytotoxic t cell , apoptosis , in situ hybridization , glial fibrillary acidic protein , granzyme , programmed cell death , immunology , cd8 , immunohistochemistry , inflammation , immune system , central nervous system , medicine , in vitro , neuroscience , perforin , gene expression , biochemistry , gene
Objective The current histopathological criteria of Rasmussen's encephalitis (RE) include the presence of T‐cell–dominated inflammation, microglial activation, neuronal loss, and astrocytic activation. An in vitro study, however, suggested glutamate receptor 3 (GluR3) antibody–mediated astrocytic loss. Therefore, we investigated astrocytic apoptosis and loss in situ. Methods Histochemical, immunohistochemical, terminal deoxynucleotidyltransferase–mediated biotin‐dUTP nick end labeling and in situ hybridization techniques were applied to paraffin sections of 20 RE cases, 6 healthy control subjects, and 6 paraneoplastic encephalomyelitis, 10 Ammon's horn sclerosis, and 5 focal cortical dysplasia cases. Results Astrocytic apoptosis and subsequent loss of these cells is a specific feature of RE. Such lesions are not found in the control groups. In RE, astrocytic apoptosis and loss was present both in cortical and in white matter areas. Astrocytes in these tissues showed major histocompatibility complex class I expression. Furthermore, granzyme‐B + lymphocytes were found in close apposition to astrocytes bordering astrocyte‐deficient lesions. Granzyme‐B + granules in these lymphocytes were polarized and faced the astrocytic membranes. No evidence was found for an antibody‐mediated destruction. Interpretation We suggest a specific attack by cytotoxic T lymphocytes as a possible mechanism responsible for astrocytic degeneration in RE. The loss of astrocytes might play a role in neuronal dysfunction, seizure induction, and enhancement of neuronal cell death. Ann Neurol 2007