title: Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis.
abstract: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder that has a broad spectrum of effects on the majority of organs, including the kidneys. Approximately 40-70% of patients with SLE will develop lupus nephritis. Renal assault during SLE is initiated by genes that breach immune tolerance and promote autoantibody production. These genes might act in concert with other genetic factors that augment innate immune signalling and IFN-I production, which in turn can generate an influx of effector leucocytes, inflammatory mediators and autoantibodies into end organs, such as the kidneys. The presence of cognate antigens in the glomerular matrix, together with intrinsic molecular abnormalities in resident renal cells, might further accentuate disease progression. This Review discusses the genetic insights and molecular mechanisms for key pathogenic contributors in SLE and lupus nephritis. We have categorized the genes identified in human studies of SLE into one of four pathogenic events that lead to lupus nephritis. We selected these categories on the basis of the cell types in which these genes are expressed, and the emerging paradigms of SLE pathogenesis arising from murine models. Deciphering the molecular basis of SLE and/or lupus nephritis in each patient will help physicians to tailor specific therapies.
authors.affiliation: Department of Bioengineering, University of Houston, 3605 Cullen Boulevard, Houston, TX 77204, USA.
authors.forename: Chandra
authors.initials: C
authors.lastname: Mohan
authors.affiliation: Division of Rheumatology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Chaim
authors.initials: C
authors.lastname: Putterman
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D007378:Interleukins / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008181:Lupus Nephritis / Q000235:genetics* / Q000276:immunology; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics; D051193:Toll-Like Receptors; D019061:src-Family Kinases / Q000235:genetics
chemical_list: D007378:Interleukins; D051193:Toll-Like Receptors; D019061:src-Family Kinases; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22
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