Elevated levels of endogenous apoptotic DNA and IFN-α in complement C4-deficient mice

Implications for induction of systemic lupus erythematosus

Doreen Finke, Katharina Randers, Robert Hoerster, Holger Hennig, Rainer Zawatzky, Tony Marion, Christian Brockmann, Katja Klempt-Giessing, Kirsten Jacobsen, Holger Kirchner, Siegfried Goerg

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Systemic lupus erythematosus (SLE), an autoimmune disease characterized by chronic nephritis, arthritis and dermatitis, and the presence of antinuclear autoantibodies, is associated with complement factor deficiencies in the classical activation pathway. In addition, IFN-α seems to be a key cytokine in SLE as an activated IFN-α system is regularly observed in patients with SLE. Here, we demonstrate that in lupus-susceptible, complement C4-deficient mice the lack of complement results in elevated intravascular levels of apoptotic DNA. The apoptotic DNA is targeted to the splenic marginal zone where it accumulates and induces IFN-α. As such, we present here a unifying hypothesis for the induction of SLE that incorporates the role of complement deficiency and elevated levels of IFN-α.

Original languageEnglish (US)
Pages (from-to)1702-1709
Number of pages8
JournalEuropean Journal of Immunology
Volume37
Issue number6
DOIs
StatePublished - Jun 1 2007

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Systemic Lupus Erythematosus
DNA
Nephritis
Dermatitis
Autoantibodies
Autoimmune Diseases
Arthritis
Cytokines
mouse C4 protein

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Elevated levels of endogenous apoptotic DNA and IFN-α in complement C4-deficient mice : Implications for induction of systemic lupus erythematosus. / Finke, Doreen; Randers, Katharina; Hoerster, Robert; Hennig, Holger; Zawatzky, Rainer; Marion, Tony; Brockmann, Christian; Klempt-Giessing, Katja; Jacobsen, Kirsten; Kirchner, Holger; Goerg, Siegfried.

In: European Journal of Immunology, Vol. 37, No. 6, 01.06.2007, p. 1702-1709.

Research output: Contribution to journalArticle

Finke, D, Randers, K, Hoerster, R, Hennig, H, Zawatzky, R, Marion, T, Brockmann, C, Klempt-Giessing, K, Jacobsen, K, Kirchner, H & Goerg, S 2007, 'Elevated levels of endogenous apoptotic DNA and IFN-α in complement C4-deficient mice: Implications for induction of systemic lupus erythematosus', European Journal of Immunology, vol. 37, no. 6, pp. 1702-1709. https://doi.org/10.1002/eji.200636719
Finke, Doreen ; Randers, Katharina ; Hoerster, Robert ; Hennig, Holger ; Zawatzky, Rainer ; Marion, Tony ; Brockmann, Christian ; Klempt-Giessing, Katja ; Jacobsen, Kirsten ; Kirchner, Holger ; Goerg, Siegfried. / Elevated levels of endogenous apoptotic DNA and IFN-α in complement C4-deficient mice : Implications for induction of systemic lupus erythematosus. In: European Journal of Immunology. 2007 ; Vol. 37, No. 6. pp. 1702-1709.
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