IdeS: a bacterial proteolytic enzyme with therapeutic potential

• Published in: PloS one 2008-02, Vol.3 (2), p.e1692-e1692
• Main Authors: Johansson, Björn P, Shannon, Oonagh, Björck, Lars
• Format: Article
• Language: English
• Subjects: Animal diseases; Animals; Antibodies; Antigens; Arthritis; Autoimmunity - drug effects; Bacteria; Bacterial Proteins - immunology; Bacterial Proteins - therapeutic use; Bands; Biochemistry/Drug Discovery; Biodegradation; Blood; Blood platelets; Calpain; Cardiovascular Disorders/Vascular Biology; Chemical bonds; Clinical Medicine; Cysteine Endopeptidases; Disease; Disease Models, Animal; Enzymes; Graft rejection; Health aspects; Hematology/Coagulation Disorders; Humans; Immunoglobulin G; Immunoglobulin G - metabolism; Immunoglobulins; Immunology/Autoimmunity; Immunology/Immunomodulation; Infections; Infectious Medicine; Infektionsmedicin; Injection; Intravenous administration; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Mice; Mortality; Pathogenesis; Pathogens; Pathology/Molecular Pathology; Proteinase; Proteins; Proteolysis; Purpura; Purpura, Thrombocytopenic, Idiopathic - drug therapy; Rabbits; Remission Induction; Rheumatology/Autoimmunity, Autoimmune, and Inflammatory Diseases; Side effects; Streptococcus infections; Streptococcus pyogenes; Streptococcus pyogenes - enzymology; Surface antigens; Thrombocytopenic purpura
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0001692

IdeS, a proteinase from Streptococcus pyogenes, cleaves immunoglobulin (Ig)G antibodies with a unique degree of specificity. Pathogenic IgG antibodies constitute an important clinical problem contributing to the pathogenesis of a number of autoimmune conditions and acute transplant rejection. To be able to effectively remove such antibodies is therefore an important clinical challenge. IdeS was found to specifically and efficiently cleave IgG in human blood in vitro (20 microg of IdeS caused a complete degradation of IgG in one ml of human whole blood in 15 minutes) and to clear IgG from the blood stream of rabbits in vivo (no IgG was detected six hours following an intravenous injection of 5 mg of IdeS) without any side effects. In a mouse model of immune thrombocytopenic purpura (ITP), polyclonal IgG antibodies against platelet surface antigens were used to induce a lethal disease. These profoundly thrombocytopenic animals were treated and cured by a single injection of IdeS. Novel information is provided concerning the IgG-cleaving activity of IdeS in vitro and in vivo. The highly specific and rapid elimination of IgG in vivo, the dramatic effect in a mouse model of ITP, and the lack of side effects in the treated animals, indicate that IdeS could also be used to treat IgG-driven diseases in humans.