Varied Immune Response to FVIII: Presence of Proteolytic Antibodies Directed to Factor VIII in Different Human Pathologies
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The versatility of antibodies is demonstrated by the various functions that they mediate such as neutralization, agglutination, fixation of the complement and its activation, and activation of effector cells. In addition to this plethora of functions, antibodies are capable of expressing enzymatic activity. Antibodies with catalytic function are a result of the productive interplay between the highly evolved machinery of the immune system and the chemical framework used to induce them (antigens). Catalytic antibodies are immunoglobulins with an ability to catalyze the reactions involving the antigen for which they are specific. Catalytic immunoglobulins of the IgM and IgG isotypes have been detected in the serum of healthy donors. In addition, catalytic immunoglobulins of the IgA isotype have been detected in the milk of healthy mothers. Conversely, antigen-specific hydrolytic antibodies have been reported in a number of inflammatory, autoimmune, and neoplastic disorders. The pathophysiological occurrence and relevance of catalytic antibodies remains a debated issue. Through the description of the hydrolysis of coagulation factor VIII as model target antigen, we propose that catalytic antibodies directed to the coagulation factor VIII may play a beneficial or a deleterious role depending on the immuno-inflammatory condition under which they occur.
KeywordsFactor VIII Anti-FVIII antibodies Catalytic antibody
This work was supported by Institut National de la Santé et de la Recherche Médicale, by Centre National de la Recherche Scientifique, by Université Pierre et Marie Curie, by the Indo-French Center for Promotion of Advanced Research, by a grant from Agence Nationale de la Recherche (ANR-05-MRAR-012) and from Japan Sciences and Technology Agency (JST, Tokyo, Japan). BW was the recipient of a research fellowship from Laboratoire Français du Fractionnement et des Biotechnologies (LFB, Les Ulis).
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