부산대학교 도서관

Objective: To report on the clearance characteristics of each cell type in response to α-galactosidase A replacement therapy (1 mg/kg biweekly) given to patients with Fabry disease. Methodology: Pre- and posttreatment renal biopsies were analyzed from 58 Fabry patients enrolled in a phase 3 double-blind, randomized, placebo-controlled trial followed by a 6-month open-label extension study of the recombinant human enzyme, α-galactosidase A. Results: Baseline evaluations revealed globotriaosylceramide (GL-3) accumulations in nearly all renal cell types, including vascular endothelial cells, vascular smooth muscle cells, mesangial cells, and interstitial cells, with particularly dense accumulations in podocytes and distal tubular epithelial cells. After 11 months of α-galactosidase A replacement therapy, there was complete clearance of glycolipid from the endothelium of all vasculature as well as from the mesangial cells of the glomerulus and interstitial cells of the cortex. Moderate clearance was noted from the smooth muscle cells of arterioles and small arteries. Podocytes and distal tubular epithelium also demonstrated evidence for decreased GL-3, although this clearance was more limited than that observed in other cell types. No evidence of immune complex disease was found by immunofluorescence, despite circulating α-galactosidase A IgG antibodies. Conclusion: A striking reversal of renal glycosphingolipid accumulation in the vasculature and in other renal cell types was observed. [ABSTRACT FROM AUTHOR]