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Characterization of multiple quinine-dependent antibodies in a patient with
episodic hemolytic uremic syndrome and immune agranulocytosis
DF Stroncek, GM Vercellotti, DE Hammerschmidt, DJ Christie, RA Shankar and HS Jacob
Department of Laboratory Medicine and Pathology, University of Minnesota
Medical School, Minneapolis.
A 23-year-old woman experienced six distinct episodes of severe combined
neutropenia and thrombocytopenia. At least one of the episodes was
accompanied by hemodialysis-requiring acute renal failure and fragmentation
hemolysis (hemolytic uremic syndrome [HUS]). In retrospect, all episodes
were probably associated with the ingestion of quinine. Quinine-dependent
antibodies to platelets, neutrophils, T lymphocytes, and red blood cells
(RBCs) were detected in the patient's serum. By a monoclonal antibody
antigen capture assay, the patient's serum contained IgG antibodies, which
in the presence, but not absence, of quinine reacted with platelet
glycoprotein (GP) complexes Ib/IX and IIb/IIIa, but not Ia/IIa. By
immunoprecipitation assay, the serum, after addition of quinine, reacted
strongly with an 85-Kd neutrophil membrane protein and weakly with 130- and
60-Kd moieties. Serum adsorbed with RBCs in the presence of quinine
continued to react with platelets and neutrophils, and serum that was
absorbed with platelets continued to react with neutrophils and RBCs,
indicating that the antigenic targets were different on platelets,
neutrophils, and RBCs. Since platelets and endothelial cells share some
antigens, we tested patient serum for antibodies to human umbilical vein
endothelial cells (HUVEC); no quinine-dependent antibodies to HUVEC were
detected. However, her quinine-dependent antibodies not only bound to
platelets and neutrophils, but also activated neutrophils. Thus, the
patient's serum with quinine aggregated neutrophils, but neither agent
alone caused activation. Moreover, the patient's serum with quinine (but
not without) augmented the adherence of neutrophils to HUVEC. Treatment of
the patient's serum with staphylococcal protein A removed the quinine
neutrophil aggregation cofactor, suggesting it was due to IgG. In both
neutrophil aggregation and adherence assays, decomplementation of the
patient's serum markedly blunted its effect. Furthermore, the patient's
serum failed to aggregate formalin-inactivated neutrophils, suggesting
neutrophil activation, probably by activated complement, was necessary for
aggregation and adhesivity to endothelium. We conclude that our patient's
neutropenia, thrombocytopenia, lymphopenia, and anemia were due to
quinine-dependent antibodies, and that these antibodies recognized epitopes
that were different in the three target cell populations. We further
suggest that HUS was likely secondary to the activation and adhesion of
neutrophils to endothelium.
Volume 80,
Issue 1,
pp. 241-248,
07/01/1992
Copyright © 1992 by The American Society of Hematology
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