Core 2N-acetylglucosaminyltransferase activity: a diagnostic marker for Wiskott-Aldrich syndrome

Abstract

Serine/threonine (O)-linked oligosaccharide on cell-surface CD43 has been reported to be abnormal in haemopoietic lineages of patients with the X-linked immunodeficiency, Wiskott-Aldrich syndrome (WAS). This defect largely appears to be the result of abnormal regulation of UDP-GlcNAc:Galβ1-3GalNAc-Rβ1-6-N-acetylglucosaminyltransferase (also known as core 2 GlcNAc-T), an enzyme in the Golgi apparatus that is subject to regulation during haemopoietic differentiation. To determine whether core 2 GlcNAc-T activity provides a reliable marker for WAS, we studied 12 unrelated WAS patients with respect to their expression of this enzyme activity. Compared with healthy subjects, the WAS patients showed levels of core 2 activity that were, on average, 2.5- and 3.9-fold higher in fresh lymphocytes and platelets respectively. These data suggest that altered core 2 GlcNAc-T activity is consistently found in lymphocytes and platelets of WAS patients and as such may provide a diagnostic marker for the disease. In view of the relatively limited amounts of blood sample generally available from infants and young children, we have also tested a more sensitive coupled assay that permits assessment of core 2 GlcNAc-T activity in very small samples of cells and which would therefore render this assay of wide clinical applicability.