Partial spectrin deficiency in hereditary pyropoikilocytosis
TL Coetzer and J Palek
Hereditary pyropoikilocytosis (HPP) is a severe hemolytic anemia in which
an instability of the red cell membrane skeleton has been correlated with
structural and functional defects of spectrin. We now report that 13
unrelated HPP subjects have approximately 30% less spectrin than normal as
evidenced by a decreased spectrin/band 3 ratio. We also examine the role of
spectrin degradation as an underlying cause of this partial spectrin
deficiency. Our studies demonstrate that the reduced spectrin content of
HPP red cells remains constant during in vivo aging of the cells in the
peripheral blood, as well as during in vitro incubation. Furthermore,
immunoblotting experiments using an affinity-purified antispectrin antibody
indicate that there is no loss of spectrin during membrane preparation and
also that neither whole HPP red cells nor ghosts nor cytosol contains any
abnormal spectrin degradation products. These data suggest that spectrin is
not degraded and that it is stable on the membrane of the circulating HPP
red cell. In contrast, however, incubation of free spectrin with a lysate
of nucleated erythroid precursor cells indicates that HPP alpha I/46
spectrin, but not HPP alpha I/74 spectrin, is more susceptible to
proteolytic degradation than a control. These data imply that the decreased
spectrin content of HPP is not due to a single defect but that a more
complex mechanism is involved. In HPP Sp alpha I/46 subjects, an increased
proteolytic degradation in bone marrow erythroid precursors of cytosolic
spectrin, prior to its assembly on the membrane, could contribute toward
the partial spectrin deficiency.
Volume 67,
Issue 4,
pp. 919-924,
04/01/1986
Copyright © 1986 by The American Society of Hematology
