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Mechanisms of immune-deposit formation and the mediation of immune renal injury

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Abstract

The passive trapping of preformed immune complexes is responsible for some forms of glomerulonephritis that are associated with mesangial or subendothelial deposits. The biochemical characteristics of circulating antigens play important roles in determining the biologic activity of immune complexes in these cases. Examples of circulating immune complex diseases include the classic acute and chronic serum sickness models in rabbits, and human lupus nephritis. Immune deposits also form “in situ”. In situ immune deposit formation may occur at subepithelial, subendothelial, and mesangial sites. In situ immune-complex formation has been most frequently studied in the Heymann nephritis models of membranous nephropathy with subepithelial immune deposits. While the autoantigenic target in Heymann nephritis has been identified as megalin, the pathogenic antigenic target in human membranous nephropathy had been unknown until the recent identification of neutral endopeptidase as one target. It is likely that there is no universal antigen in human membranous nephropathy. Immune complexes can damage glomerular structures by attracting circulating inflammatory cells or activating resident glomerular cells to release vasoactive substances, cytokines, and activators of coagulation. However, the principal mediator of immune complex-mediated glomerular injury is the complement system, especially C5b-9 membrane attack complex formation. C5b-9 inserts in sublytic quantities into the membranes of glomerular cells, where it produces cell activation, converting normal cells into resident inflammatory effector cells that cause injury. Excessive activation of the complement system is normally prevented by a series of circulating and cell-bound complement regulatory proteins. Genetic deficiencies or mutations of these proteins can lead to the spontaneous development of glomerular disease. The identification of specific antigens in human disease may lead to the development of fundamental therapies. Particularly promising future therapeutic approaches include selective immunosuppression and interference in complement activation and C5b-9-mediated cell injury.

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Authors and Affiliations

  1. Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1 Bunkyo-ku, Tokyo, 113-8655, Japan

    Masaomi Nangaku

  2. Division of Nephrology, University of Washington, Seattle, WA, USA

    William G. Couser

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  1. Masaomi Nangaku
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  2. William G. Couser
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Correspondence to Masaomi Nangaku.

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Nangaku, M., Couser, W. Mechanisms of immune-deposit formation and the mediation of immune renal injury. Clin Exp Nephrol 9, 183–191 (2005). https://doi.org/10.1007/s10157-005-0357-8

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  • DOI: https://doi.org/10.1007/s10157-005-0357-8

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