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Netting neutrophils in autoimmune small-vessel vasculitis


Small-vessel vasculitis (SVV) is a chronic autoinflammatory condition linked to antineutrophil cytoplasm autoantibodies (ANCAs). Here we show that chromatin fibers, so-called neutrophil extracellular traps (NETs), are released by ANCA-stimulated neutrophils and contain the targeted autoantigens proteinase-3 (PR3) and myeloperoxidase (MPO). Deposition of NETs in inflamed kidneys and circulating MPO-DNA complexes suggest that NET formation triggers vasculitis and promotes the autoimmune response against neutrophil components in individuals with SVV.

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Figure 1: ANCA-induced formation of NETs containing autoantigens PR3 and MPO.
Figure 2: In vivo evidence for NET formation in individuals with SVV.


  1. Jennette, J.C. & Falk, R.J. N. Engl. J. Med. 337, 1512–1523 (1997).

    Article  CAS  Google Scholar 

  2. Kallenberg, C.G.M., Heeringa, P. & Stegeman, C.A. Nat. Clin. Pract. Rheumatol. 2, 661–670 (2006).

    Article  CAS  Google Scholar 

  3. Falk, R.J., Terrell, R.S., Charles, L.A. & Jennette, J.C. Proc. Natl. Acad. Sci. USA 87, 4115–4119 (1990).

    Article  CAS  Google Scholar 

  4. Pfister, H. et al. Blood 104, 1411–1418 (2004).

    Article  CAS  Google Scholar 

  5. Xiao, H. et al. J. Clin. Invest. 110, 955–963 (2002).

    Article  CAS  Google Scholar 

  6. Brinkmann, V. et al. Science 303, 1532–1535 (2004).

    Article  CAS  Google Scholar 

  7. Clark, S.R. et al. Nat. Med. 13, 463–469 (2007).

    Article  CAS  Google Scholar 

  8. Fuchs, T.A. et al. J. Cell Biol. 176, 231–241 (2007).

    Article  CAS  Google Scholar 

  9. Harper, L., Ren, Y., Savill, J., Adu, D. & Savage, C.O.S. Am. J. Pathol. 157, 211–220 (2000).

    Article  CAS  Google Scholar 

  10. Yousefi, S. et al. Nat. Med. 14, 949–953 (2008).

    Article  CAS  Google Scholar 

  11. Murao, S., Stevens, F.J., Ito, A. & Huberman, E. Proc. Natl. Acad. Sci. USA 85, 1232–1236 (1988).

    Article  CAS  Google Scholar 

  12. Lande, R. et al. Nature 449, 564–569 (2007).

    Article  CAS  Google Scholar 

  13. Woltman, A.M. et al. Kidney Int. 71, 1001–1008 (2007).

    Article  CAS  Google Scholar 

  14. Wenzel, J. et al. J. Pathol. 205, 435–442 (2005).

    Article  CAS  Google Scholar 

  15. Holdenrieder, S. et al. Ann. NY Acad. Sci. 1075, 318–327 (2006).

    Article  CAS  Google Scholar 

  16. Leadbetter, E.A. et al. Nature 416, 603–607 (2002).

    Article  CAS  Google Scholar 

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We would like to thank W. Samtleben for providing serum samples, R. Bittner for technical assistance and E. Csernok and A. Kniepert for help with serum samples. Moreover, we are grateful to M. Sixt and E. Meinl for helpful suggestions and H. Wekerle for his constant interest and support of this work. We also thank M. Monestier (Temple University) for providing us with histone-specific monoclonal antibody and G. Koch (University of Freiburg) for the kind gift of the antibody specific for MxA. This work was funded by the Deutsche Forschungsgemeinschaft (SFB 571). It was further supported by the US National Institutes of Health (AI053194) and by fellowships from the Susan G. Komen for the Cure Foundation and the Alexander von Humboldt Foundation.

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Authors and Affiliations



K.K. performed most of the experiments. M.K. performed IFN-α ELISA and contributed to data analysis and discussion. U.S., W.B. and W.L.G. provided patient material and clinical data. Z.W. provided critical input on data analysis. H.-J.G. provided kidney biopsies and clinical data. H.-J.G. and V.B. performed immunostainings and analysis of histology. K.K. and D.E.J. designed and supervised the study, analyzed data and wrote the manuscript. D.E.J. secured the funding. All authors discussed results and commented on the manuscript.

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Correspondence to Kai Kessenbrock or Dieter E Jenne.

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Supplementary Figs. 1–7, Supplementary Tables 1 and 2 and Supplementary Methods (PDF 821 kb)

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Kessenbrock, K., Krumbholz, M., Schönermarck, U. et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med 15, 623–625 (2009).

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