title: Toward Clinical use of the IgG Specific Enzymes IdeS and EndoS against Antibody-Mediated Diseases.
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 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.
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Biomedical Center B14, SE-221 84, Lund, Sweden. mattias.collin@med.lu.se.
authors.forename: Mattias
authors.initials: M
authors.lastname: Collin
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Biomedical Center B14, SE-221 84, Lund, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Björck
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology*; D015551:Autoimmunity / Q000187:drug effects*; D001426:Bacterial Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006026:Glycoside Hydrolases / Q000494:pharmacology / Q000627:therapeutic use*; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism*; D059748:Proteolysis; D016896:Treatment Outcome
chemical_list: D001426:Bacterial Proteins; D007074:Immunoglobulin G; C442815:Mac-1-like protein, Streptococcus; D006026:Glycoside Hydrolases
keywords: Autoimmunity; Glycan hydrolysis; Glycosylation; Immune evasion; Immunoglobulins; Proteases; Transplant rejection