REVIEWPhysiopathology of catalytic antibodies: the case for factor VIII-hydrolyzing immunoglobulin GWootla, Bharatha; Dasgupta, Suryasarathia; Mallet, Vincentb; Kazatchkine, Michel Da; Nagaraja, Valakunjac; Friboulet, Alaind; Kaveri, Srinivas Va; Lacroix-Desmazes, Sébastiena Author Information aINSERM UMRS 681, Universite Pierre & Marie Curie (UPMC-Paris 6)/Institut des cordeliers, France bCochin Institute and Hepatology Service, Necker Hospital, Paris, France cDepartment of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India dUMR CNRS 6022, Compiègne University of Technology (UTC), Compiègne, France Received 27 September, 2005 Revised 12 February, 2006 Accepted 14 February, 2006 Correspondence and requests for reprints to Sébastien Lacroix-Desmazes, INSERM U681, Biomedical Research Centre of Cordeliers, 15 rue de l'Ecole de Médecine, 75006, Paris, France E-mail: [email protected] Sponsorship: The present work was supported by Insitut National de la Santé et de la Recherche Médicale, by Centre National de la Recherche Scientifique, by Université Pierre et Marie Curie (UPMC Paris 6), by the Indo-French Center for Promotion of Advanced Research (CEFIPRA), and a grant from Bayer Pharma (Clayton, North Carolina, USA). B.W. is the recipient of a fellowship from the Laboratoire Français de Fractionnement et de Biotechnologie (Les Ulis, France). Suryasarathi Dasgupta is the recipient of a fellowship from CEFIPRA and from FRM. Blood Coagulation & Fibrinolysis: June 2006 - Volume 17 - Issue 4 - p 229-234 doi: 10.1097/01.mbc.0000224840.40839.5a Buy Metrics Abstract Antibodies that are able to catalyze the antigen for which they are specific are produced spontaneously by the immune system. Catalytic immunoglobulins (Igs) both of the IgM and IgG isotypes have been detected in the serum of healthy donors, where they have been proposed to participate in the removal of metabolic waste and in the defense of the organism against invading pathogens. Conversely, antigen-specific hydrolytic IgG have been reported in a number of inflammatory, autoimmune and neoplastic disorders: their pathogenic effects have been demonstrated occasionally. The pathophysiological relevance of catalytic antibodies thus remains an elusive issue. Through the description of the pro-coagulation factor VIII as a model target antigen for catalytic antibodies, we propose that catalytic antibodies have either a beneficial or a deleterious role depending on the physiopathological context. Physiology thus relies on a delicate equilibrium between the levels of soluble target antigen and that of antigen-specific hydrolyzing immunoglobulins. Indeed, in patients with hemophilia A, in whom endogenous factor VIII is deficient or missing and exogenous factor VIII needs to be administered to treat hemorrhagic events, the development of factor VIII-hydrolyzing IgG that inactivate the therapeutically administered factor VIII, may reveal deleterious. In contrast, in a situation in which excess factor VIII may be detrimental and lead to excessive coagulation, disseminated thrombosis and organ ischemia, as seen in severe sepsis, our recent data suggest that the presence of factor VIII-hydrolyzing IgG may be beneficial to the patient. © 2006 Lippincott Williams & Wilkins, Inc.