Journal
BLOOD
Volume 109, Issue 6, Pages 2470-2476Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-04-018093
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Funding
- NHLBI NIH HHS [R01 HL067347, HL67347-01] Funding Source: Medline
- NIAID NIH HHS [R01 AI060687, AI60687] Funding Source: Medline
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The present work evaluated antibody-coated liposomes as a new treatment strategy for immune thrombocytopenic purpura (ITP) through the use of a mouse model of the disease. Effects of anti-methotrexate antibody (AMI)-coated liposomes and intravenous immunoglobulin (IVIG)-coated liposomes (15, 30, 60 mu mol lipid/kg) were compared with the effects of IVIG (0.4, 1, 2 g/kg) and anti-red blood cell (anti-RBC) monoclonal antibody immunotherapy (TER119, 5, 15, 25, and 50 mu g/mouse) on MWReg30-induced thrombocytopenia. Each treatment was found to attenuate thrombocytopenia in a dose-dependent manner and, consistent with previous work, IVIG was found to increase antiplatelet antibody clearance in a dose-dependent manner. TER119 demonstrated greater effects on thrombocytopenia relative to other therapies (peak platelet counts: 224% +/- 34% of initial platelet counts for 50 mu g TER119/mouse versus 160% +/- 34% for 2 g/kg IVIG, 88% +/- 36% for 60 mu mol lipid/kg AMI-coated liposomes, and 80% +/- 25% for 60 mu mol lipid/kg IVIG-coated liposomes). However, the effects of TER119 were associated with severe hemolysis, as TER119 decreased RBC counts by approximately 50%. The present work demonstrated that antibody-coated liposomes attenuated thrombocytopenia in this model at a much lower immunoglobulin dose than that required for IVIG effects and, in contrast with TER119, antibody-coated liposomes increased platelet counts without altering RBC counts.
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