Lymphoblastoid cell lines, transformed by Epstein-Barr virus, in the enzymatic study of hereditary lysosomal storage diseases.

Abstract

Assay conditions were studied for 8 lysosomal enzymes in lymphoblastoid cell lines transformed by Epstein-Barr virus. The transformed lymphoblastoid cells retained all 8 enzyme activities, though the levels sometimes differed from those in the peripheral lymphocytes or granulocytes. The levels of these 8 lysosomal enzymes were measured in lymphoblastoid cells from 11 patients with hereditary lysosomal storage diseases, GMI-gangliosidosis, a variant of .beta.-galactosidase deficiency (sialidase deficiency with a partial .beta.-galactosidase deficiency), Tay-Sachs disease, Gaucher disease, Hurler syndrome, Scheie syndrome and I-cell disease, and from 20 of their obligate heterozygotes. No activity of enzymes that were deficient in the respective disease, except I-cell disease, was detected in the lymphoblastoid cells from the patient. In I-cell disease, the cells showed lower levels of some enzyme activities. .beta.-D-Galactosidase activity from heterozygotes of the patient with GMI-gangliosidosis and .alpha.-L-iduronidase activity from heterozygotes of the patient with Hurler syndrome were in carrier range. On Sephadex G-150 gel filtration, .beta.-D-galactosidase in control material gave 2 peaks (I and II). In GMI-gangliosidosis, peak II was absent and peak I was markedly diminished. Peak II in the heterozygotes was smaller than that of control. On DEAE cellulose column chromatography of hexoaminidase, 2 major isoenzymes (hexosaminidase A and B) were detected in control. Hexosaminidase A was not detected in Tay-Sachs disease, and the ratios of hexosaminidase (Hex) A/Hex B in the parents were lower than those in control.