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New insights into the pathogenesis of IgA nephropathy

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Abstract

IgA nephropathy (IgAN) is the most common diagnosis amongst primary glomerular diseases in most countries where renal biopsies are regularly performed. Only a fraction of these patients is at high risk of losing glomerular filtration rate (GFR) in particular those with high grade proteinuria, uncontrolled hypertension or already impaired GFR at diagnosis, and those with renal scars in the renal biopsy. Genetic modifiers of IgAN onset and/or course are emerging. Spontaneous animal models of IgAN are problematic given considerable species differences between the rodent and human IgA system. However, new transgenic models help to better understand the pathogenesis. A key pathogenetic role appears to be played by underglycated IgA1 as well as autoantibodies to these IgA glycoforms and IgA receptors such as CD89 and transferrin receptor 1. Once IgA and/or IgA-containing immune complexes are deposited or formed in the mesangium, secondary effector mechanisms become important including complement activation, release of mesangial growth factors (in particular platelet-derived growth factor), and finally non-IgAN-specific events that culminate in glomerular and subsequently renal tubulointerstitial scaring. Here, we review these processes and describe potential novel therapeutic targets in IgAN.

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Acknowledgments

This work was supported by Deutsche Forschungsgemeinschaft SFB TRR57 P25 to JF, Agence nationale pour la recherche (ANR JCJC 2010), Fundaçao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) (INSERM/FAPESP grant), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) (CNPq/INSERM grant), and USP/COFECUB to ICM.

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Authors and Affiliations

  1. Division of Nephrology, RWTH University Hospital Aachen, 52057, Aachen, Germany

    Jürgen Floege

  2. INSERM U699, Paris, France

    Ivan C. Moura

  3. Université Paris Diderot, Sorbonne Paris Cité, Paris, France

    Ivan C. Moura

  4. Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands

    Mohamed R. Daha

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  1. Jürgen Floege
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  2. Ivan C. Moura
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  3. Mohamed R. Daha
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Correspondence to Jürgen Floege.

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This article is a contribution to the special issue on Immunopathology of Glomerular Diseases - Guest Editors: P. Ronco and J. Floege

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Floege, J., Moura, I.C. & Daha, M.R. New insights into the pathogenesis of IgA nephropathy. Semin Immunopathol 36, 431–442 (2014). https://doi.org/10.1007/s00281-013-0411-7

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