Blocking of experimental arthritis by cleavage of IgG antibodies in vivo.
OBJECTIVE
To investigate whether IgG-degrading enzyme of Streptococcus pyogenes (IdeS), a bacterial cysteine endopeptidase that cleaves human IgG in the hinge region, can be used for blocking the development of arthritis.


METHODS
Recombinant IdeS was purified and tested for specificity against mouse IgG. IdeS was injected intravenously into mice with collagen antibody-induced arthritis (CAIA), collagen-induced arthritis (CIA), or relapsing CIA, and its effects on arthritis development and severity were assessed.


RESULTS
IdeS efficiently cleaved mouse IgG2a/c and IgG3 in vitro. Even at low dosage (10 microg), IdeS specifically cleaved IgG2a in vivo without any apparent side effects. IdeS treatment efficiently blocked CAIA induced by IgG2a antibodies. No effect was observed when arthritis was induced with IgG2b anti-type II collagen antibodies; since IdeS does not cleave IgG2b, this indicated that IgG cleavage was the mechanism of action. IdeS treatment reduced the severity of arthritis if administered within 24 hours after the onset of clinical arthritis, but did not block ongoing severe arthritis. IdeS treatment also significantly prevented an antibody-induced relapse in mice that had chronic arthritis, and delayed the onset and reduced the severity of arthritis in classic CIA.


CONCLUSIONS
IdeS has therapeutic potential in IgG antibody-mediated autoimmune arthritis, representing a new and unique means of blocking pathogenic antibodies.
Nandakumar
Kutty Selva
KS
Lund University, Lund, Sweden. nan@med.lu.se
Johansson
Björn P
BP
Björck
Lars
L
Holmdahl
Rikard
R
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001426:Bacterial Proteins / Q000378:metabolism*; D002908:Chronic Disease; D007074:Immunoglobulin G / Q000378:metabolism*; D051379:Mice; D055502:Secondary Prevention; D013297:Streptococcus pyogenes / Q000201:enzymology*
D001426:Bacterial Proteins; D007074:Immunoglobulin G; C442815:Mac-1-like protein, Streptococcus