The IgG-specific endoglycosidase EndoS inhibits both cellular and complement-mediated autoimmune hemolysis.
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.
Allhorn
Maria
M
Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden. maria.allhorn@med.lu.se
Briceño
Juana G
JG
Baudino
Lucie
L
Lood
Christian
C
Olsson
Martin L
ML
Izui
Shozo
S
Collin
Mattias
M
D000744:Anemia, Hemolytic, Autoimmune / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism / Q000494:pharmacology*; D015922:Complement C1q / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D007518:Isoantibodies / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D011817:Rabbits; D018029:Rho(D) Immune Globulin
D001426:Bacterial Proteins; D007074:Immunoglobulin G; D016209:Interleukin-8; D007518:Isoantibodies; C061961:RHO(D) antibody; D018029:Rho(D) Immune Globulin; D015922:Complement C1q; D006026:Glycoside Hydrolases; C431325:NDOS protein, Streptococcus pyogenes; D010100:Oxygen