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Vasculitis syndromes

Silence is golden as epigenetic mechanisms are blamed for autoantigen expression in ANCA vasculitis

Nature Reviews Rheumatology volume 6, page 614 (2010)Cite this article

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PR3 and MPO are granule proteins whose genes are normally only expressed during neutrophil development; they are silent in healthy mature neutrophils. However, PR3 and MPO messenger RNAs are present in mature neutrophils from patients with ANCA vasculitis; if these transcripts are translated into protein, the availability of these autoantigens could increase. Are the PR3 and MPO genes actively transcribed in ANCA neutrophils, and could their overexpression result from failed epigenetic silencing? Ciavatta et al. set out to investigate.

The researchers examined whether histone modifications associated with epigenetic silencing were depleted in PR3 and MPO from ANCA neutrophils compared to those from healthy controls. A CpG island in MPO from ANCA cells was unmethylated. Furthermore, levels of trimethylation at lysine 27 of histone H3 were reduced at the two loci in ANCA cells. The group discovered that this deficiency stemmed from both failed methylation and aberrant demethylation mechanisms, which potentially underpin the etiology of ANCA vasculitis.

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References

ORIGINAL RESEARCH PAPER

  1. Ciavatta, D. J. et al. Epigenetic basis for aberrant upregulation of autoantigen genes in humans with ANCA vasculitis. J. Clin. Invest. 120, 3209–3219 (2010)

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FURTHER READING

  1. Chen, M. & Kallenberg, C. G. M. ANCA-associated vasculitides—advances in pathogenesis and treatment. Nat. Rev. Rheumatol. 6, 653–664 (2010)

    Article  CAS  Google Scholar 

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Authors
  1. Emma Leah
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Leah, E. Silence is golden as epigenetic mechanisms are blamed for autoantigen expression in ANCA vasculitis. Nat Rev Rheumatol 6, 614 (2010). https://doi.org/10.1038/nrrheum.2010.168

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  • DOI: https://doi.org/10.1038/nrrheum.2010.168

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