Blood, 1974, Vol. 44, No. 5, pp. 629-637.
© 1974 American Society of Hematology, Inc.
Complement-independent Clearance of IgG-sensitized
Erythrocytes: Inhibition by Cortisone
John P. Atkinson 1 and
Michael M. Frank 1
1 Laboratory of Clinical Investigation, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, Md. 20014.
The effect of corticosteroid administration
on the complement-independent clearance
of IgG-sensitized erythrocytes was examined in guinea pigs. 51Cr-labeled
guinea pig erythrocytes coated with a
known amount of high-avidity IgG antibody were injected into control and
cortisone-treated C4-deficient guinea pigs,
and cell survival was determined. In these
animals with a genetically controlled total
deficiency of the fourth complement component, cell-bound antibody does not
activate the biologically active complement components; clearance is therefore
complement independent. At low levels of
sensitization, cortisone completely inhibited the splenic sequestration of IgG
coated red cells. As the amount of antibody coating the red cell was increased,
higher cortisone doses were required to
decrease the rate and magnitude of
clearance. Eventually a level of erythrocyte sensitization was reached where
cortisone did not significantly alter the
clearance pattern compared to untreated
controls. The cortisone effect was present
by 3 days but required 5-7 days before it
was maximal. No evidence was found to
suggest that cortisone decreased the affinity of the antibody for the red cell membrane. Rather, the most likely explanation
for these results is that cortisone affects the
interaction between IgG on the erythrocyte
surface and its receptor on splenic and
hepatic macrophages. This experimental
model of immune hemolytic anemia
parallels those cases of warm-antibody-mediated disease in which complement
plays no role. These findings suggest that
a major clinical effect of cortisone therapy
may be to decrease complement-independent erythrocyte clearance, thereby inducing a remission even in the presence
of a positive antiglobulin test.
Submitted on February 26, 1974
Accepted on May 24, 1974
