Chemically dimerized intravenous immunoglobulin has potent ameliorating activity in a mouse immune thrombocytopenic purpura model.
High-dose intravenous immunoglobulin (IVIG) preparations are currently used for the treatment of autoimmune diseases such as immune thrombocytopenic purpura (ITP). Although the mechanisms of IVIG efficacy remain enigmatic, some clinical and laboratory studies suggest that interaction of the Fc domain of IgG, especially the Fc domain of dimeric IgG, with its receptors (Fc gamma receptors; FcγRs) plays an essential role. In this study, IVIG was dimerized with chemical crosslinkers to augment its therapeutic efficacy. Dimerized IVIG was found to have a much higher affinity for FcγRs than monomeric IVIG. In a mouse ITP model, chemically dimerized IVIG abrogated the decrease in platelet numbers in the blood that was caused by an anti-platelet antibody at a dose that was one tenth of the required dose of IVIG. These results suggest that chemical dimerization of IVIG should greatly improve the efficacy of IVIG therapy of ITP.
Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki 2641, Noda, Chiba 278-8510, Japan. yusuke.machino@kyowa-kirin.co.jp
Yusuke
Y
Machino
Emiko
E
Suzuki
Saki
S
Higurashi
Hiroto
H
Ohta
Mami
M
Suzuki
Junya
J
Kohroki
Yasuhiko
Y
Masuho
D000818:Animals; D000941:Antigens / Q000276:immunology; D003432:Cross-Linking Reagents / Q000737:chemistry; D004195:Disease Models, Animal; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage* / Q000737:chemistry* / Q000276:immunology; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000737:chemistry* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D055503:Protein Multimerization; D011696:Purpura, Thrombocytopenic / Q000628:therapy*; D017452:Receptors, IgG / Q000737:chemistry / Q000276:immunology
D000941:Antigens; D003432:Cross-Linking Reagents; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D017452:Receptors, IgG