Autologous IgM, IgA, and complement binding to sickle erythrocytes in vivo.
Evidence for the existence of dense sickle cell subsets
GA Green
Department of Medicine, University of Southern California School of
Medicine, Los Angeles 90033.
We have previously reported that sickle erythrocytes sedimenting at high
specific density after gradient centrifugation exhibit increased IgG
binding in vivo as compared with low-density paired samples. We have
performed the present study to determine whether the opsonization of dense
sickle cells in vivo could also involve autologous IgM, IgA, and
complement. IgA, IgM, and complement binding in vivo to the surface of
density-separated sickle erythrocytes was detected by flow cytometric
analyses. IgM and complement C3 fragment binding was detected primarily on
high-density sickle erythrocytes. With the exception outlined below, IgA
binding was detected for all sickle cell fractions that sediment at
densities > 1.085 g/mL. IgM, IgA, and complement C3 fragment binding was
increased on high-density sickle erythrocytes as compared with low-density
paired samples and exceeded that binding to normal erythrocytes by 30% +/-
10% (mean +/- range), 50% +/- 10%, and 41% +/- 5%, respectively. Two-color
flow cytometry indicates that high-density sickle cell fractions contain at
least two heterogeneous RBC subsets. One is an RBC subset that binds IgA in
combination with IgM and C3, and the second subset is devoid of IgA yet
binds IgM and C3. These findings indicate that high-density sickle cells
exhibit a greater heterogeneity than has been reported in previous studies,
which is based on autologous Ig binding in vivo; and suggest that RBC
components of this most severely dehydrated sickle cell subpopulation could
have heterogeneous origin and pathophysiologic significance. Although the
functional role of IgA binding to human RBCs is unclear, our findings that
IgM and complement bind to the same high- density sickle cell fractions
suggest that both the IgM and the sickle erythrocyte-bound IgG determined
in previous studies could mediate the deposition of complement on dense
sickle cells in vivo. These findings support the hypotheses that
irreversibly sickled cell-enriched high- density sickle RBC subpopulations
could be removed from the circulation by erythrocyte phagocytosis that is
enhanced by the presence of complement.
Volume 82,
Issue 3,
pp. 985-992,
08/01/1993
Copyright © 1993 by The American Society of Hematology
