The population of paroxysmal nocturnal hemoglobinuria neutrophils deficient
in decay-accelerating factor is also deficient in alkaline phosphatase
SF Burroughs, DV Devine, G Browne and ME Kaplan
Section of Hematology/Oncology, Veterans Administration Medical Center,
Minneapolis, MN 55417.
In patients with paroxysmal nocturnal hemoglobinuria (PNH) the RBCs,
neutrophils (PMNs), monocytes, and platelets derived from the abnormal
clone are deficient in the complement-regulatory protein decay-
accelerating factor (DAF). RBC acetylcholinesterase (AChE) and leukocyte
alkaline phosphatase (LAP) activities are also characteristically low. DAF,
AChE, and LAP are known to be anchored within cell membranes to
glycophospholipid-containing phosphatidylinositol (PI). Because PNH
progenitors contain DAF that appears to be lost with maturation, it has
been proposed that this disorder results from abnormal tethering of these
and possibly other proteins to membrane PI. We were puzzled, therefore,
that our two PNH patients consistently had normal LAP levels. Consequently,
we studied their isolated PMNs to compare DAF and LAP activities in
individual cells. PMNs were separated by flow cytometry into DAF-positive
and - negative populations by using rabbit anti-DAF antiserum and
fluorescein- conjugated goat antirabbit IgG. In both patients the majority
of PMNs were DAF deficient, and these cells contained very little alkaline
phosphatase activity. In contrast, the smaller, DAF-positive cell
populations were phosphatase replete. This is the first demonstration that
abnormalities in DAF and LAP activity occur in the same PNH PMN population
and strengthens the hypothesis that defective anchoring of proteins to
membrane glycophospholipid underlies the pathophysiology of this disorder.
Volume 71,
Issue 4,
pp. 1086-1089,
04/01/1988
Copyright © 1988 by The American Society of Hematology
