Glial fibrillary acidic protein and S-100 protein in human hepatic encephalopathy: Immunocytochemical demonstration of dissociation of two glia-associated proteins

Summary

Immunocytochemical staining patterns for glial fibrillary acidic protein (GFAP) and S-100 protein (S100P) were compared in cerebral cortex, basal ganglia and white matter of eight cases with hepatic encephalopathy (HE), including four cases of Wilson's disease and four of liver cirrhosis, and of eight age-matched controls, using the peroxidase-antiperoxidase method on adjacent paraffin sections. The majority of Alzheimer type II glia (Alzg II) showed prominent immunoreactivity for S100P but not for GFAP, resembling normal astrocytes of protoplasmic type; Alzg II might be interpreted as being peculiar types of reactive astrocytes retaining characteristics of protoplasmic astrocytes. A small number of Alzg II cells showed slight perinuclear immunoreactivity for GFAP; some lacked both markers. This suggests a spectrum of metabolic changes in these two proteins in Alzg II. GFAP-positive Alzg II cells were restricted to basal ganglia and white matter adjacent to grey matter, indicating that expression of GFAP in Alzg II might be modulated by local factors. Alzheimer type I cells and Opalski cells in Wilson's disease were immunoreactive for both proteins, confirming their astroglial origin and different character from that of Alzg II. In morphometric comparison, the proportion of GFAP-positive glial cells decreased in the cortex (P<0.001) but not significantly in the white matter (0.05<P<0.1), confirming earlier data that the prominent reduction of GFAP in HE brains is restricted to the grey matter. In the putamen, the proportion of GFAP-positive glia decreased in acquired HE (0.01<P<0.05) but not in Wilson's disease, probably resulting from prominent fibrous glial poliferation related to severe parenchymal damage in Wilson's disease. In contrast, glial cells immunoreactive for S100P did not significantly change (P>0.1) in any of the areas studied, indicating an intact glial metabolism of S100P in HE. This clear dissociation between GFAP and S100P defines Alzg II as a peculiar glial reaction with a rather selective deficit of GFAP metabolism (“gliofibrillary dystrophy”).