Blocking of experimental arthritis by cleavage of IgG antibodies in vivo

摘要: 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 development arthritis. Methods. Recombinant IdeS was purified and tested specificity against mouse IgG. injected intravenously into mice with collagen antibody-induced arthritis (CAIA), collagen-induced (CIA), or relapsing CIA, its effects on severity were assessed. Results. efficiently cleaved IgG2a/c IgG3 vitro. Even at low dosage (10 mu g), specifically IgG2a vivo without any apparent side effects. treatment blocked CAIA induced by antibodies. No effect observed when IgG2b anti-type 11 antibodies; since does not cleave IgG2b, this indicated cleavage mechanism action. reduced if administered within 24 hours after onset clinical arthritis, but did block ongoing severe also significantly prevented an relapse had chronic delayed classic CIA. Conclusion. has therapeutic potential antibody-mediated autoimmune representing new unique means pathogenic (Less)