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Immunopathogenesis of IgAN

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Abstract

The defining hallmark of IgA nephropathy (IgAN) is deposition of polymeric IgA1 in the glomerular mesangium accompanied by a mesangial proliferative glomerulonephritis. The mechanisms involved in mesangial polymeric IgA1 deposition and the initiation of inflammatory glomerular injury remain unclear. This lack of a complete understanding of the pathogenesis of IgAN has meant that there is still no treatment known to modify mesangial deposition of IgA. Increasing evidence, however, supports the importance of IgA-containing immune complex formation as a pivotal factor driving mesangial IgA deposition and triggering of glomerular injury. A number of potentially important changes to the IgA1 molecule have been identified in IgAN, which may contribute to immune complex formation. These changes suggest that the polymeric IgA1 that deposits in IgA nephropathy is derived from mucosally primed plasma cells. The presence of this IgA in the circulation reflects displacement of mucosal B lineage cells to systemic sites and may be the result of mishoming of lymphocytes trafficking along the mucosa–bone marrow axis.

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Authors and Affiliations

  1. John Walls Renal Unit, Leicester General Hospital, Leicester, LE4 5PW, UK

    Jonathan Barratt, Alice C. Smith, Karen Molyneux & John Feehally

  2. Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK

    Jonathan Barratt, Alice C. Smith, Karen Molyneux & John Feehally

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Barratt, J., Smith, A.C., Molyneux, K. et al. Immunopathogenesis of IgAN. Semin Immunopathol 29, 427–443 (2007). https://doi.org/10.1007/s00281-007-0089-9

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