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A novel pathogenetic concept—antiviral immunity in lupus nephritis

Nature Reviews Nephrology volume 8, pages 183–189 (2012)Cite this article

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Abstract

Lupus nephritis is a complication of systemic lupus erythematosus, a heterogeneous autoimmune syndrome involving multiple pathways. Accumulating data from the fields of genetics, clinical science, transcriptomics and basic immunology indicate that antiviral immunity has relevance in the pathogenesis of lupus nephritis. This idea is based on the existence of genetic variants that promote the persistence of nuclear particles in the extracellular space or inside lysosomes. Such nuclear particles mimic viral particles and their RNA or DNA components activate viral nucleic acid recognition receptors in antigen-presenting cells. These autoadjuvant effects of endogenous nucleic acids promote an inappropriate immune interpretation of the nuclear particles during antigen presentation. This process fosters the expansion of autoreactive T cells and B cells, which promotes autoantibody production and immune complex glomerulonephritis. The release of interferon α sets off an antiviral immune response with a coordinated induction of hundreds of antiviral genes both inside and outside the kidney. In this article we summarize the available data indicating that innate immunity triggers antiviral immunity in systemic lupus erythematosus. We also discuss the related implications for innovative therapeutic strategies.

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Figure 1: Possible pathogenetic mechanisms of murine and/or human lupus.
Figure 2: How extracellular nuclear particles mimic viral particles to activate similar immune responses.
Figure 3: Mechanisms by which antiviral immunity might drive lupus nephritis.

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Acknowledgements

A. Migliorini is a graduate of the Deutsche Forschungsgemeinschaft Graduate College 1202. H.-J. Anders is supported by the Deutsche Forschungsgemeinschaft via AN372/9-2, 10-1, and 11-1.

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  1. Department of Nephrology, Medizinische Poliklinik, Klinikum der Universität München, Pettenkoferstrasse 8a, Munich, 80336, Germany

    Adriana Migliorini & Hans-Joachim Anders

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A. Migliorini and H.-J. Anders contributed equally to all aspects of this manuscript.

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Correspondence to Hans-Joachim Anders.

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Migliorini, A., Anders, HJ. A novel pathogenetic concept—antiviral immunity in lupus nephritis. Nat Rev Nephrol 8, 183–189 (2012). https://doi.org/10.1038/nrneph.2011.197

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