On the mechanisms of sensitization and attachment of antibodies to RBC in
drug-induced immune hemolytic anemia
A Salama and C Mueller-Eckhardt
The mechanisms of sensitization and attachment of drug-dependent antibodies
to RBC in drug-induced immune hemolytic anemias are largely speculative.
Nomifensine has been incriminated in causing immune hemolysis in a large
number of patients. The hemolysis was usually of the so-called immune
complex type, less commonly of the autoimmune type, and more surprisingly,
few patients had developed both types of hemolysis. To determine whether
nomifensine (metabolite)-dependent antibodies (ndab) exhibit specificity
for antigenic structures of RBC membranes, 30 ndab were tested against
large panels of RBC with common and rare antigens. We found that only 14
out of 30 ndab were invariably reactive with all cells tested. Nine
antibodies were, similar to the majority of idiopathic or drug-induced
autoantibodies, not or only weakly reactive with Rhnull RBC. Three
antibodies did not react with cord RBC and could be inhibited by soluble I
antigen. The remaining four antibodies gave inhomogeneous reaction patterns
or were even negative with selected RBC; their specificity could not be
identified. On a Scatchard plot analysis of one ndab, a maximum of 173,000
drug- dependent antibodies of the IgG class can specifically bind per RBC
in the presence of the drug. Although nomifensine and its metabolites do
not attach tightly onto RBC, our results clearly indicate that RBC do not
act as "innocent bystanders," but rather serve as a surface for a loose
attachment of drugs that possibly cause a subtle structural change in the
cell antigens and, by this means, allow in vivo sensitization; and a
specific binding of the resultant antibodies. This concept would explain
why these antibodies can be directed against drug- cell complexes, against
cell antigens alone (autoantibodies), or against both in the same patient.
Volume 69,
Issue 4,
pp. 1006-1010,
04/01/1987
Copyright © 1987 by The American Society of Hematology
