title: Complement and autoimmunity.
abstract: The complement system is a component of the innate immune system. Its main function was initially believed to be limited to the recognition and elimination of pathogens through direct killing or stimulation of phagocytosis. However, in recent years, the immunoregulatory functions of the complement system were demonstrated and it was determined that the complement proteins play an important role in modulating adaptive immunity and in bridging innate and adaptive responses. When the delicate mechanisms that regulate this sophisticated enzymatic system are unbalanced, the complement system may cause damage, mediating tissue inflammation. Dysregulation of the complement system has been involved in the pathogenesis and clinical manifestations of several autoimmune diseases, such as systemic lupus erythematosus, vasculitides, Sjögren's syndrome, antiphospholipid syndrome, systemic sclerosis, dermatomyositis, and rheumatoid arthritis. Complement deficiencies have been associated with an increased risk to develop autoimmune disorders. Because of its functions, the complement system is an attractive therapeutic target for a wide range of diseases. Up to date, several compounds interfering with the complement cascade have been studied in experimental models for autoimmune diseases. The main therapeutic strategies are inhibition of complement activation components, inhibition of complement receptors, and inhibition of membrane attack complex. At present, none of the available agents was proven to be both safe and effective for treatment of autoimmune diseases in humans. Nonetheless, data from preclinical studies and initial clinical trials suggest that the modulation of the complement system could constitute a viable strategy for the treatment of autoimmune conditions in the decades to come.
authors.affiliation: Rheumatology, Allergology and Clinical Immunology, Department of Internal Medicine, Unit of Rheumatology, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Ballanti
authors.forename: Carlo
authors.initials: C
authors.lastname: Perricone
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Greco
authors.forename: Marta
authors.initials: M
authors.lastname: Ballanti
authors.forename: Gioia
authors.initials: G
authors.lastname: Di Muzio
authors.forename: Maria Sole
authors.initials: MS
authors.lastname: Chimenti
authors.forename: Roberto
authors.initials: R
authors.lastname: Perricone
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy*; D015551:Autoimmunity; D003167:Complement Activation / Q000187:drug effects; D015938:Complement Membrane Attack Complex / Q000037:antagonists & inhibitors; D003165:Complement System Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007113:Immunity, Innate; D007167:Immunotherapy / Q000379:methods*; D011951:Receptors, Complement / Q000037:antagonists & inhibitors; D012306:Risk
chemical_list: D000893:Anti-Inflammatory Agents; D015938:Complement Membrane Attack Complex; D011951:Receptors, Complement; D003165:Complement System Proteins