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BIOLOGICAL SCIENCES / MEDICAL SCIENCES
IgG glycan hydrolysis by a bacterial enzyme as a therapy against autoimmune conditions
Division of Infection Medicine, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden
Edited by Emil C. Gotschlich, The Rockefeller University, New York, NY, and approved January 22, 2008 (received for review November 29, 2007)
EndoS from Streptococcus pyogenes efficiently hydrolyzes the functionally important and conserved N-linked glycan of IgG in human blood. Repeated i.v. administration of EndoS in rabbits completely hydrolyzes the glycans of the whole IgG pool, despite the generation of anti-EndoS antibodies. EndoS administration had no apparent effects on the health of the animals. EndoS hydrolysis of the IgG glycan has profound effects on IgG effector functions, such as complement activation and Fc receptor binding, suggesting that the enzyme could be used as an immunomodulatory therapeutic agent against IgG-mediated diseases. We demonstrate here that EndoS indeed has a protective effect in a mouse model of lethal IgG-driven immune (or idiopathic) thrombocytopenic purpura. EndoS pretreatment of pathogenic antibodies inhibits the development of disease, and the enzyme also rescues mice from already established disease when severe thrombocytopenia and s.c. bleeding have developed. These results identify EndoS as a potential therapeutic agent against diseases where pathogenic IgG antibodies are important and further emphasize antibody glycans as possible targets in future therapies against antibody-mediated autoimmune conditions.
autoimmunity | immunomodulation | Streptococcus pyogenes | endoglycosidase | glycosylation
Author contributions: M.C., O.S., and L.B. designed research; M.C. and O.S. performed research; O.S. contributed new reagents/analytic tools; M.C., O.S., and L.B. analyzed data; and M.C. wrote the paper.
Conflict of interest statement: Hansa Medical, which funded this study in part, has filed a patent application on the in vivo use of EndoS. M.C., O.S., and L.B. are listed as inventors, and the application is pending.
This article is a PNAS Direct Submission.
See Commentary on page 4081.
*To whom correspondence should be addressed. E-mail: mattias.collin{at}med.lu.se
© 2008 by The National Academy of Sciences of the USA
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  C. N. Scanlan, D. R. Burton, and R. A. Dwek Making autoantibodies safe PNAS, March 18, 2008; 105(11): 4081 - 4082. [Full Text] [PDF]
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