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Pathogenesis of idiopathic IgA nephropathy

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Abstract

Despite a prodigious amount of work on the physiology of IgA production in man, and many studies on the immunopathology of IgA nephropathy, ranging from the immunogenetics to the immune response to chemical characteristics of the IgA, we are hardly any nearer to defining the pathogenesis of this disease. One of the main changes in our understanding has been to recognise that the bone marrow, now known to produce normally one-third of the body's IgA, overproduces this immunoglobulin in IgA nephropathy. This alters the previous notion that IgA nephropathy was due simply to IgA production in the mucosa, although a mucosal component is not excluded. Certain characteristics of the IgA in the diseased kidney and the circulation have been defined: it is of subclass IgA1 and has a higher proportion of λ light chains and negative charge than in normal subjects. The specificities of the IgA, either in the kidney or in complexes, have not helped to clarify the pathogenesis. They have been found for a wide range of endogenous and exogenous antigens, suggesting that the antibody activity represents polyclonal B cell activation. These findings have not helped to confirm the prevailing theory that IgA nephropathy is an immune complex disease. Other theories put forward are that IgA nephropathy is an autoimmune disease, glomerular components or IgA itself being among the candidate antigens, or that there is primary dysregulation of the IgA immune system. At this stage of development in our understanding of this common nephropathy, it is important to guard against the assumption that idiopathic IgA nephropathy is one disease and is the result of a single pathogenetic mechanism.

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  1. Renal Unit and Division of Medicine, United Medical and Dental Schools, Guy's Hospital, 4th Floor, Hunt's House, SE1 9RT, London, UK

    D. Gwyn Williams

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Williams, D.G. Pathogenesis of idiopathic IgA nephropathy. Pediatr Nephrol 7, 303–311 (1993). https://doi.org/10.1007/BF00853230

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