title: The alternative pathway of complement and the thrombotic microangiopathies.
abstract: Thrombotic microangiopathies (TMA) are disorders defined by microangiopathic hemolytic anemia, non-immune thrombocytopenia and have multi-organ involvement including the kidneys, brain, gastrointestinal, respiratory tract and skin. Emerging evidence points to the central role of complement dysregulation in leading to microvascular endothelial injury which is crucial for the development of TMAs. This key insight has led to the development of complement-targeted therapy. Eculizumab is an anti-C5 monoclonal antibody, which has revolutionized the treatment of atypical hemolytic uremic syndrome. Several other anti-complement therapeutic agents are currently in development, offering a potential armamentarium of therapies available to treat complement-mediated TMAs. The development of sensitive, reliable and easy to perform assays to monitor complement activity and therapeutic efficacy will be key to devising an individualized treatment regime with the potential of safely weaning or discontinuing treatment in the appropriate clinical setting.
authors.affiliation: Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada; Research Institute, Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Chia Wei
authors.initials: CW
authors.lastname: Teoh
authors.affiliation: Research Institute, Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Riedl
authors.affiliation: Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada; Research Institute, Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada. Electronic address: christoph.licht@sickkids.ca.
authors.forename: Christoph
authors.initials: C
authors.lastname: Licht
mesh_terms: D000743:Anemia, Hemolytic / Q000097:blood / Q000150:complications / Q000188:drug therapy; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D006801:Humans; D013921:Thrombocytopenia / Q000097:blood / Q000150:complications / Q000188:drug therapy; D057049:Thrombotic Microangiopathies / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C481642:eculizumab
keywords: Alternative complement pathway; Atypical hemolytic uremic syndrome; Eculizumab; Thrombotic microangiopathy; Treatment monitoring