Genetic Susceptibility to Kidney Disease as a Consequence of Systemic Autoimmunity

Andrew Wang, Chandra Mohan, Edward K. Wakeland

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

This chapter focuses on the genetic basis of lupus nephritis caused by systemic lupus erythematosus (SLE) disease and discusses the overall features of the disease, the current understanding of the role of genetics in susceptibility, and the role of genetic epistasis in the development of severe kidney pathology. There are six classes of lupus nephritis defined by WHO guidelines that essentially describe a continuum of disease. Class I and II nephritis belong to the "benign" category, class III and IV lupus have transitioned to pathogenic autoimmunity, and class V lupus nephritis is defined as membranous proliferative glomerulonephritis. The WHO classifies patients with advanced, chronic disease, extensive glomerular scarring, and renal insufficiency as having class VI lupus nephritis. Genetic analysis of SLE susceptibility in humans has progressed significantly over the past few years and several disease alleles have been identified. The most robust associations detected in genetic analyses have been with deficiencies in the C2, C4, and C1q components of the complement system. Several genetic studies indicate that 45% of all white SLE patients are homozygous or heterozygous for defective alleles of complement component C4a, indicating that even small deficiencies in this component may be an important component of disease progression. Lupus nephritis is thought to be initiated by deposition of preformed circulating immune complexes (IC) in the glomerular capillary wall. ICs may preferentially deposit in mesangial, subendothelial, or subepithelial sites as they vary widely in both their stereochemical properties and serum concentrations.

Original languageEnglish (US)
Title of host publicationGenetic Diseases of the Kidney
PublisherElsevier Inc.
Pages737-748
Number of pages12
ISBN (Print)9780124498518
DOIs
Publication statusPublished - 2009

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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