title: C1q, autoimmunity and apoptosis.
abstract: Deficiency of classical pathway complement components displays a hierarchical association with the development of systemic lupus erythematosus (SLE). Individuals with deficiency of C1q, the first component of the classical pathway of activation, have the highest prevalence of SLE and the most severe manifestations of the disease. However, complement is also implicated in the effector inflammatory phase of the autoimmune response that characterizes SLE. Complement proteins are deposited in inflamed tissues causing consumption of complement. In addition, autoantibodies to C1q develop as part of the autoantibody response. Understanding how C1q deficiency results in the autoimmune phenotype of SLE may provide valuable clues to the role of the complement system in the maintenance of immune tolerance. In this review firstly we discuss the relationship between C1q deficiency and/or consumption and lupus. Secondly, we consider the links between apoptosis and complement. Finally we review the lessons we have learned from a murine model of C1q deficiency discussing the experimental evidence in support of the hypothesis that C1q may critically influence the immune response to self-antigens contained within the surface blebs generated by apoptotic cells.
authors.affiliation: Division of Medicine, Faculty of Medicine, Imperial College, London, UK.
authors.forename: Marina
authors.initials: M
authors.lastname: Botto
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Walport
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies; D015551:Autoimmunity / Q000276:immunology*; D003167:Complement Activation; D015922:Complement C1q / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D003171:Complement Pathway, Classical / Q000502:physiology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D015922:Complement C1q