Abstract:
: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.
journal_name
Bloodjournal_title
Bloodauthors
Jordan MB,van Rooijen N,Izui S,Kappler J,Marrack Pdoi
10.1182/blood-2001-11-0061subject
Has Abstractpub_date
2003-01-15 00:00:00pages
594-601issue
2eissn
0006-4971issn
1528-0020pii
2001-11-0061journal_volume
101pub_type
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