Immunoelectron-microscopic detection of globotriaosylceramide accumulated in the skin of patients with Fabry disease.

Summary Background  Fabry disease is characterized by the systemic accumulation of glycosphingolipids, particularly in the lysosomes of vascular endothelial cells of most organs due to the deficient activity of α-galactosidase A. The major glycolipid accumulated in tissue is globotriaosylceramide (GL-3). To date, no direct detection of GL-3 by immunoelectron microscopy has been reported. Objectives  To examine whether GL-3 is accumulated exclusively in lysosomes of cutaneous cells using an anti-GL-3 monoclonal antibody (mAb) and immunoelectron microscopy. Methods  Skin specimens from seven patients with Fabry disease were examined immunohistochemically by light and electron microscopy using an anti-GL-3 mAb. Results  By light microscopy, the cytoplasm of vascular endothelial cells, eccrine gland cells, and perineurium was stained with mouse anti-GL-3 antibody. Electron microscopically, positive signals for GL-3 were limited to dilated lysosomes in the cytoplasm of endothelial cells, pericytes, eccrine gland cells, dermal fibroblasts and perineurium. Conclusions  Our results demonstrate that the cytoplasmic deposit in Fabry disease was GL-3 and the accumulated GL-3 was localized essentially to lysosomes.