Advanced

Toward clinical use of the IgG specific enzymes IdeS and EndoS against antibody-mediated diseases

Collin, Mattias LU and Björck, Lars LU (2017) In Methods in Molecular Biology 1535. p.339-351
Abstract

The endoglycosidase EndoS and the protease IdeS from the human pathogen Streptococcus pyogenes are immunomodulating enzymes hydrolyzing human IgG. IdeS cleaves IgG in the lower hinge region, while EndoS hydrolyzes the conserved N-linked glycan in the Fc region. Both enzymes are remarkably specific for human IgG that after hydrolysis loses most of its effector functions, such as binding to leukocytes and complement activation, all contributing to bacterial evasion of adaptive immunity. However, taken out of their infectious context, we and others have shown that IdeS and EndoS can alleviate autoimmune disease in a number of animal models of antibody-mediated disorders. In this chapter, we will briefly describe the discovery and... (More)

The endoglycosidase EndoS and the protease IdeS from the human pathogen Streptococcus pyogenes are immunomodulating enzymes hydrolyzing human IgG. IdeS cleaves IgG in the lower hinge region, while EndoS hydrolyzes the conserved N-linked glycan in the Fc region. Both enzymes are remarkably specific for human IgG that after hydrolysis loses most of its effector functions, such as binding to leukocytes and complement activation, all contributing to bacterial evasion of adaptive immunity. However, taken out of their infectious context, we and others have shown that IdeS and EndoS can alleviate autoimmune disease in a number of animal models of antibody-mediated disorders. In this chapter, we will briefly describe the discovery and characterization of these unique enzymes, present the findings from a number of animal models of autoimmunity where the enzymes have been tested, and outline the ongoing clinical testing of IdeS. Furthermore, we will discuss the rationale for further development of IdeS and EndoS into novel pharmaceuticals against diseases where IgG antibodies contribute to the pathology, including, but not restricted to, chronic and acute autoimmunity, transplant rejection, and antidrug antibody reactions.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
keywords
Autoimmunity, Glycan hydrolysis, Glycosylation, Immune evasion, Immunoglobulins, Proteases, Transplant rejection
in
Methods in Molecular Biology
volume
1535
pages
13 pages
publisher
Humana Press
external identifiers
  • scopus:85005950992
ISSN
10643745
DOI
10.1007/978-1-4939-6673-8_23
language
English
LU publication?
yes
id
e8c5ecc3-317f-4fed-8fbd-0a529f5a39ac
date added to LUP
2017-03-16 14:08:08
date last changed
2018-06-17 05:21:40
@inbook{e8c5ecc3-317f-4fed-8fbd-0a529f5a39ac,
  abstract     = {<p>The endoglycosidase EndoS and the protease IdeS from the human pathogen Streptococcus pyogenes are immunomodulating enzymes hydrolyzing human IgG. IdeS cleaves IgG in the lower hinge region, while EndoS hydrolyzes the conserved N-linked glycan in the Fc region. Both enzymes are remarkably specific for human IgG that after hydrolysis loses most of its effector functions, such as binding to leukocytes and complement activation, all contributing to bacterial evasion of adaptive immunity. However, taken out of their infectious context, we and others have shown that IdeS and EndoS can alleviate autoimmune disease in a number of animal models of antibody-mediated disorders. In this chapter, we will briefly describe the discovery and characterization of these unique enzymes, present the findings from a number of animal models of autoimmunity where the enzymes have been tested, and outline the ongoing clinical testing of IdeS. Furthermore, we will discuss the rationale for further development of IdeS and EndoS into novel pharmaceuticals against diseases where IgG antibodies contribute to the pathology, including, but not restricted to, chronic and acute autoimmunity, transplant rejection, and antidrug antibody reactions.</p>},
  author       = {Collin, Mattias and Björck, Lars},
  issn         = {10643745},
  keyword      = {Autoimmunity,Glycan hydrolysis,Glycosylation,Immune evasion,Immunoglobulins,Proteases,Transplant rejection},
  language     = {eng},
  pages        = {339--351},
  publisher    = {Humana Press},
  series       = {Methods in Molecular Biology},
  title        = {Toward clinical use of the IgG specific enzymes IdeS and EndoS against antibody-mediated diseases},
  url          = {http://dx.doi.org/10.1007/978-1-4939-6673-8_23},
  volume       = {1535},
  year         = {2017},
}