title: A review of human diseases caused or exacerbated by aberrant complement activation.
abstract: Complement is the backbone of our innate immune system. It is of ancient evolutionary origin, being traced back to horseshoe crabs 350 million years ago. It consists today of more than 25 proteins which must work together like clockwork to distinguish friend from foe. Self-attack by the complement system can occur whenever it fails to do so. This failure has been reported to occur in an estimated 22 human diseases. A significant number of these are chronic degenerative neurological disorders. In some, there is overwhelming evidence that complement self-attack causes the disease. In many others, it is considered only to contribute to the overall pathology. Finding effective therapeutic agents should be a high priority for medical research. To date, the monoclonal antibody eculizumab is the only approved agent. Molecules under development include other monoclonal antibodies directed at C5, C3, and properdin, various aptamers to C3, and small molecules that are orally available.
authors.affiliation: Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: mcgeerpl@mail.ubc.ca.
authors.forename: Patrick L
authors.initials: PL
authors.lastname: McGeer
authors.affiliation: Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Moonhee
authors.initials: M
authors.lastname: Lee
authors.affiliation: Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Edith G
authors.initials: EG
authors.lastname: McGeer
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D002908:Chronic Disease; D003167:Complement Activation / Q000276:immunology*; D003170:Complement Pathway, Alternative / Q000235:genetics; D003171:Complement Pathway, Classical / Q000235:genetics; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000276:immunology; D058990:Molecular Targeted Therapy; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D010300:Parkinson Disease / Q000235:genetics / Q000276:immunology; D011951:Receptors, Complement
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011951:Receptors, Complement; C481642:eculizumab
keywords: Complement; Complement receptors; Complement-mediated diseases; Membrane attack complex