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

Allhorn, Maria LU ; Briceño, Juana G; Baudino, Lucie; Lood, Christian LU ; Olsson, Martin L LU ; Izui, Shozo and Collin, Mattias LU (2010) In Blood 115(24). p.5080-5088
Abstract
EndoS from Streptococcus pyogenes is an immunomodulating enzyme that specifically hydrolyzes glycans from human IgG 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, i.e. phagocytosis, complement activation and hemolysis in vitro and in vivo was inhibited by EndoS. Phagocytosis by monocytes in vitro was inhibited by pre-treatment of anti-D with EndoS before sensitization of RBC, and abrogated by direct addition of EndoS to blood containing sensitized... (More)
EndoS from Streptococcus pyogenes is an immunomodulating enzyme that specifically hydrolyzes glycans from human IgG 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, i.e. phagocytosis, complement activation and hemolysis in vitro and in vivo was inhibited by EndoS. Phagocytosis by monocytes in vitro was inhibited by pre-treatment of anti-D with EndoS before sensitization of RBC, and abrogated by direct addition of EndoS to blood containing sensitized RBC. The toxic effects of monocytes stimulated with anti-D-sensitized RBC, as measured by interleukin-8 secretion and oxygen metabolite production, was restrained by EndoS. Agglutination of RBC and complement mediated hemolysis in vitro in whole human blood caused by rabbit anti-RBC was inhibited by EndoS. Development of anemia in mice caused by a murine anti-RBC IgG2a 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 RBC. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
115
issue
24
pages
5080 - 5088
publisher
American Society of Hematology
external identifiers
  • wos:000278888900018
  • pmid:20357243
  • scopus:77954680167
ISSN
1528-0020
DOI
10.1182/blood-2009-08-239020
language
English
LU publication?
yes
id
77726d1d-536a-4288-a057-e0ebdbdcafe6 (old id 1598705)
alternative location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2890147/
date added to LUP
2010-05-03 09:18:12
date last changed
2018-05-29 11:04:50
@article{77726d1d-536a-4288-a057-e0ebdbdcafe6,
  abstract     = {EndoS from Streptococcus pyogenes is an immunomodulating enzyme that specifically hydrolyzes glycans from human IgG 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, i.e. phagocytosis, complement activation and hemolysis in vitro and in vivo was inhibited by EndoS. Phagocytosis by monocytes in vitro was inhibited by pre-treatment of anti-D with EndoS before sensitization of RBC, and abrogated by direct addition of EndoS to blood containing sensitized RBC. The toxic effects of monocytes stimulated with anti-D-sensitized RBC, as measured by interleukin-8 secretion and oxygen metabolite production, was restrained by EndoS. Agglutination of RBC and complement mediated hemolysis in vitro in whole human blood caused by rabbit anti-RBC was inhibited by EndoS. Development of anemia in mice caused by a murine anti-RBC IgG2a 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 RBC.},
  author       = {Allhorn, Maria and Briceño, Juana G and Baudino, Lucie and Lood, Christian and Olsson, Martin L and Izui, Shozo and Collin, Mattias},
  issn         = {1528-0020},
  language     = {eng},
  number       = {24},
  pages        = {5080--5088},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {The IgG specific endoglycosidase EndoS inhibits both cellular and complement mediated autoimmune hemolysis.},
  url          = {http://dx.doi.org/10.1182/blood-2009-08-239020},
  volume       = {115},
  year         = {2010},
}