title: The etiology of glomerulonephritis: roles of infection and autoimmunity.
abstract: Despite major advances in understanding genetic predispositions ('first hits'), pathogenic immune responses, and the mediators of tissue injury in glomerulonephritis (GN), there remains a dearth of knowledge about the etiologic events, or 'second hits', which trigger these diseases. This paper reviews evidence that infections initiate most forms of GN through numerous simultaneous and/or sequential pathways that begin with activation of the innate immune response and lead to autoimmunity. These pathways include immune dysregulation, adjuvant or bystander effects, epitope spreading, molecular mimicry, epitope conformational changes, and antigen complementarity that, in genetically susceptible individuals, result in the nephritogenic autoimmune responses that underlie GN. Infections may also have direct effects on glomerular cells. Rapid expansion in knowledge of the microbiome and its role in health and disease, as well as systems biology approaches to glomerular disease offer the potential to develop preventive approaches to GNs that can now be treated only with immunosuppression.
authors.affiliation: Division of Nephrology, Department of Medicine, The University of Washington, Seattle, Washington, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Couser
authors.affiliation: Division of Nephrology, Department of Medicine, University of Colorado, Denver, Colorado, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D001424:Bacterial Infections / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D003165:Complement System Proteins / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005921:Glomerulonephritis / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000382:microbiology / Q000821:virology; D064307:Microbiota; D012307:Risk Factors; D014777:Virus Diseases / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000821:virology
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D001323:Autoantibodies; D003165:Complement System Proteins