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Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies

Nature Genetics volume 19, pages 56–59 (1998)Cite this article

Abstract

The complement system plays a paradoxical role in the development and expression of autoimmunity in humans. The activation of complement in systemic lupus erythematosus (SLE) contributes to tissue injury. In contrast, inherited deficiency of classical pathway components, particularly C1q (ref. 1), is powerfully associated with the development of SLE. This leads to the hypothesis that a physiological action of the early part of the classical pathway protects against the development of SLE (ref. 2) and implies that C1q may play a key role in this respect. C1q-deficient (C1qa−/−) mice were generated by gene targeting and monitored for eight months. C1qa−/− mice had increased mortality and higher litres of autoantibodies, compared with strain-matched controls. Of the Clqa−/− mice, 25% had glomerulonephritis with immune deposits and multiple apoptotic cell bodies. Among mice without glomerulonephritis, there were significantly greater numbers of glomerular apoptotic bodies in C1q-deficient mice compared with controls. The phenotype associated with C1q deficiency was modified by background genes. These findings are compatible with the hypothesis that C1q deficiency causes autoimmunity by impairment of the clearance of apoptotic cells.

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Authors and Affiliations

  1. Rheumatology Section, Hammersmith Campus, Imperial College School of Medicine, London, W12 ONN, UK

    Marina Botto, Chiara Dell' Agnola, Anne E. Bygrave & Mark J. Walport

  2. Department of Histopathology, St Mary's Campus, London, W2 1NY, UK

    E. Mary Thompson

  3. Department of Histopathology, Hammersmith Campus, Imperial College School of Medicine, London, W12 ONN, UK

    H. Terence Cook

  4. Institute of Medical Microbiology and Hygiene, 55101, Mainz, Germany

    Franz Petry & Michael Loos

  5. Department of Human Genetics, Memorial Sloan Kettering Cancer Center, New York, New York, 10021, USA

    Pier Paolo Pandolfi

Authors
  1. Marina Botto
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  2. Chiara Dell' Agnola
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  6. Franz Petry
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  7. Michael Loos
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  8. Pier Paolo Pandolfi
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  9. Mark J. Walport
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Correspondence to Mark J. Walport.

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Botto, M., Dell' Agnola, C., Bygrave, A. et al. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet 19, 56–59 (1998). https://doi.org/10.1038/ng0598-56

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