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Prepublished online as a Blood First Edition Paper on August 29, 2002; DOI 10.1182/blood-2001-11-0061.
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Blood, 15 January 2003, Vol. 101, No. 2, pp. 594-601
IMMUNOBIOLOGY
Liposomal clodronate as a novel agent for treating autoimmune
hemolytic anemia in a mouse model
Michael B. Jordan,
Nico van Rooijen,
Shozo Izui,
John Kappler, and
Philippa Marrack
From the Department of Immunology, and the Howard
Hughes Medical Institute, National Jewish Medical and Research
Center, and the Departments of Pediatrics, Medicine, Pharmacology, and
Biochemistry and Molecular Genetics, University of Colorado Health
Science Center, Denver; the Department of Cell Biology and Immunology,
Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands;
and the Department of Pathology, University of Geneva, Geneva,
Switzerland.
Autoimmune hemolytic anemia (AIHA) is a disease in which
autoantibodies against red blood cells (RBCs) lead to their premature destruction. Most clinically significant autoantibodies are of the
immunoglobulin G (IgG) type, which leads primarily to the uptake and destruction of RBCs by splenic and hepatic macrophages. Therapies such as corticosteroids and splenectomy are directed at
interfering with this process. Liposomally encapsulated clodronate (dichloromethylene diphosphonate) has previously been found to be a
potent antimacrophage agent. It selectively depletes animals of
macrophages within 24 hours of administration by inducing
apoptosis in these cells. Therefore, we hypothesized that
liposomal clodronate would be a useful agent for treating AIHA. We
tested this hypothesis in a mouse model of AIHA in which animals were
given either anti-RBC antibodies or preopsonized RBCs. In either case,
liposomal clodronate substantially decreased RBC destruction. This drug
formulation was effective within hours by first blocking and
then depleting phagocytic macrophages, and its action lasted for 1 to 2 weeks. Thus, in AIHA, liposomal clodronate therapy may act like a
temporary, medicinal splenectomy. As such, it may prove useful
in situations where rapid response to therapy is critical or other
medical therapies are inadequate.
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