Renal immunology and pathology: Edited by Agnes B. FogoGoodpasture's disease: molecular architecture of the autoantigen provides clues to etiology and pathogenesisPedchenko, Vadima; Vanacore, Robertoa; Hudson, Billya,b,cAuthor Information aDivision of Nephrology and Hypertension, Department of Medicine, USA bDepartment of Pathology, USA cDepartment of Biochemistry, Vanderbilt University Medical Center, Nashville, Tennessee, USA Correspondence to Vadim Pedchenko, PhD, Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, S-3221 MCN, 1161 21st Avenue South, Nashville, TN 37232-2372, USA Tel: +1 615 322 7299; e-mail: [email protected] Current Opinion in Nephrology and Hypertension: May 2011 - Volume 20 - Issue 3 - p 290-296 doi: 10.1097/MNH.0b013e328344ff20 Buy Metrics Abstract Purpose of review Goodpasture's disease is an autoimmune disorder characterized by the deposition of pathogenic autoantibodies in basement membranes of kidney and lung, which induces rapidly progressive glomerulonephritis and pulmonary hemorrhage. The target antigen is the α3NC1 domain of collagen IV, which is expressed in target organs as an α345 network. Recent studies of specificity and epitopes of Goodpasture's autoantibodies and discovery of novel posttranslational modification of the antigen, a sulfilimine bond, provide further insight into mechanisms of initiation and progression of Goodpasture's disease. Recent findings Analysis of the specificity of Goodpasture's autoantibodies revealed a distinct subset of circulating and kidney-bound antiα5NC1 antibody, which is associated with loss of kidney function. Structural integrity of the α345NC1 hexamer is stabilized by the novel sulfilimine crosslinks conferring immune privilege to the Goodpasture's autoantigen. Native antibodies may contribute to establishment of immune tolerance to autoantigen. Structural analysis of epitopes for autoantibodies and alloantibodies indicates a critical role of conformational change in the α345NC1 hexamer in eliciting an autoimmune response in Goodpasture's disease. Summary Understanding of the quaternary structure of the Goodpasture's autoantigen continues to provide insights into autoimmune mechanisms that serve as a basis for development of novel diagnostic tools and therapies for Goodpasture's disease. © 2011 Lippincott Williams & Wilkins, Inc.