title: Genetics of Lupus Nephritis: Clinical Implications.
abstract: Systemic lupus erythematosus is a heterogeneous autoimmune disease marked by the presence of pathogenic autoantibodies, immune dysregulation, and chronic inflammation that may lead to increased morbidity and early mortality from end-organ damage. More than half of all systemic lupus erythematosus patients will develop lupus nephritis. Genetic-association studies have identified more than 50 polymorphisms that contribute to lupus nephritis pathogenesis, including genetic variants associated with altered programmed cell death and defective immune clearance of programmed cell death debris. These variants may support the generation of autoantibody-containing immune complexes that contribute to lupus nephritis. Genetic variants associated with lupus nephritis also affect the initial phase of innate immunity and the amplifying, adaptive phase of the immune response. Finally, genetic variants associated with the kidney-specific effector response may influence end-organ damage and the progression to end-stage renal disease and death. This review discusses genetic insights of key pathogenic processes and pathways that may lead to lupus nephritis, as well as the clinical implications of these findings as they apply to recent advances in biologic therapies.
authors.affiliation: Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Munroe
authors.affiliation: Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK; Oklahoma Clinical and Translational Science Institute; Departments of Medicine & Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK. Electronic address: jamesj@omrf.org.
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D008181:Lupus Nephritis / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies
keywords: SLE; genetics; immune response; lupus nephritis