Lesion pathology predicts response to plasma exchange in secondary progressive MS.
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Adult↗
Biomedical subjects
W Brueck
Publications and source records attributed to W Brueck.
Expression of major histocompatibility complex class I molecules on the different cell types in multiple sclerosis lesions.
Multiple sclerosis is considered to be an immune-mediated disease of the central nervous system, characterized by chronic inflammation, primary demyelination and axonal damage. The mechanisms of demyelination and axonal injury are heterogeneous and complex. One possible mechanism is direct damage of oligodendrocytes and neurons by Class I MHC restricted cytotoxic T-cells. In this study we analyzed the expression of functional MHC class I molecule complex, consisting of alpha-chain and beta2-microglobulin, in a large sample of human autopsy material, containing 10 cases of acute MS, 10 cases of chronic active MS, 10 cases of chronic inactive MS and 21 controls. To examine the expression of MHC class I and II molecules on the different cell-types in brain, we used quantitative immunohistochemical techniques, double staining and confocal laser microscopy scans on paraffin embedded sections. We found constitutive expression of MHC class I molecule on microglia and endothelial cells. A hierarchical up-regulation of MHC class I was present on astrocytes, oligodendrocytes, neurons and axons, depending upon the severity of the disease and the activity of the lesions. MHC class II molecules were expressed on microglia and macrophages, but not on astrocytes. These data indicate that in MS lesions all cells of the central nervous system are potential targets for Class I MHC restricted cytotoxic T-cells.
Adult↗
Multiple sclerosis: lessons from neuropathology.
The focus of multiple sclerosis (MS) research has been on attempts to identify the specific pathogenic mechanism responsible for producing the multifocal central nervous system inflammatory demyelinating lesions. However, extensive in vitro and in vivo evidence suggests that multiple different immunological mechanisms may produce the typical demyelinated plaque. A detailed examination of actively demyelinating MS lesions reveals a profound heterogeneity in the structural and immunopathological patterns of demyelination and oligodendrocyte pathology between different MS patients, suggesting multiple pathogenic mechanisms may contribute to oligodendrocyte and myelin injury in MS. These observations raise the question whether MS may be a neurological syndrome with different immunopathological mechanisms triggering a common pathway rather than a single disease with a uniform mechanism of myelin destruction. With the advent of new tools for neurobiological and immunological research applied to actively demyelinated MS lesions, an opportunity exists to reevaluate MS neuropathology. This review highlights the spectrum of the inflammatory demyelinating diseases, the multitude of effector mechanisms that may produce myelin destruction, and the pathologic heterogeneity observed in MS lesions. A careful evaluation of MS neuropathology should provide important clues regarding the induction, target, evolution, and pathogenesis of this complex disease.
Autoantibodies↗