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The IgG-specific endoglycosidase EndoS inhibits both cellular and complement-mediated autoimmune hemolysis

Allhorn, Maria
Briceno, J. G.
Lood, Christian
Olsson, M. L.
Collin, Mattias
Published in Blood. 2010, vol. 115, no. 24, p. 5080-5088
Abstract EndoS from Streptococcus pyogenes is an immunomodulating enzyme that specifically hydrolyzes glycans from human immunoglobulin G and thereby affects antibody effector functions. Autoimmune hemolytic anemia is caused by antibody-mediated red blood cell (RBC) destruction and often resists treatment with corticosteroids that also cause frequent adverse effects. We show here that anti-RhD (anti-D) and rabbit anti-human-RBC antibodies (anti-RBC) mediated destruction of RBC, ie, phagocytosis, complement activation, and hemolysis in vitro and in vivo was inhibited by EndoS. Phagocytosis by monocytes in vitro was inhibited by pretreatment of anti-D with EndoS before sensitization of RBCs and abrogated by direct addition of EndoS to blood containing sensitized RBCs. The toxic effects of monocytes stimulated with anti-D-sensitized RBCs, as measured by interleukin-8 secretion and oxygen metabolite production, was restrained by EndoS. Agglutination of RBCs and complement-mediated hemolysis in vitro in whole human blood caused by rabbit anti-RBCs was inhibited by EndoS. Development of anemia in mice caused by a murine anti-RBC immunoglobulin G2a monoclonal autoantibody and complement activation and erythrophagocytosis by Kupffer cells in the liver were reduced by EndoS. Our data indicate that EndoS is a potential therapeutic agent that might be evaluated as an alternative to current treatment regimens against antibody-mediated destruction of RBCs.
Keywords *Anemia, Hemolytic, Autoimmune/drug therapy/immunology/metabolismAnimalsBacterial Proteins/metabolism/*pharmacologyComplement C1q/metabolismErythrocytes/drug effects/immunology/metabolismGlycoside Hydrolases/metabolism/*pharmacologyHemolysis/*drug effects/*immunologyHumansImmunoglobulin G/immunology/*metabolismInterleukin-8/metabolismIsoantibodies/immunology/metabolismMiceMice, Inbred BALB CMonocytes/drug effects/immunology/metabolismOxygen/metabolismPhagocytosis/drug effects/immunologyRabbits
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PMID: 20357243
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