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Type I interferon-mediated autoinflammation due to DNase II deficiency

Mathieu Rodéro 1 Alessandra Tesser 2 Eva Bartok 3 Gillian Rice 4 Erika Della Mina Marine M Depp Benoit Beitz 5 Vincent Bondet 6 Nicolas Cagnard 7 Darragh Duffy 6 Michael Dussiot 8 Marie-Louise Frémond Marco Gattorno 9 Flavia Guillem 8 Naoki Kitabayashi 8 Fabrice Porcheray 5 Frederic Rieux-Laucat 8 Luis Seabra Carolina Uggenti Stefano Volpi 10 Leo Zeef 11 Marie-Alexandra Alyanakian 12 Jacques Beltrand 8 Anna Monica Bianco 2 Nathalie Boddaert 13 Chantal Brouzes 14 Sophie Candon Roberta Caorsi Marina Charbit 15 Monique Fabre 16 Flavio Faletra Muriel Girard Annie Harroche Evelyn Hartmann Dominique Lasne 14 Annalisa Marcuzzi Bénédicte Neven 12 Patrick Nitschke 17 Tiffany Pascreau Serena Pastore Capucine Picard 18 Paolo Picco Elisa Piscianz Michel Polak 19 Pierre Quartier 12 Marion Rabant 20 Gabriele Stocco 21 Andrea Taddio Florence Uettwiller Erica Valencic Diego Vozzi Gunther Hartmann 22 Winfried Barchet Olivier Hermine 23 Brigitte Bader-Meunier 12 Alberto Tommasini 24 Yanick Crow 4, 1 
Abstract : Microbial nucleic acid recognition serves as the major stimulus to an antiviral response, implying a requirement to limit the misrepresentation of self nucleic acids as non-self and the induction of autoinflammation. By systematic screening using a panel of interferon-stimulated genes we identify two siblings and a singleton variably demonstrating severe neonatal anemia, membranoproliferative glomerulonephritis, liver fibrosis, deforming arthropathy and increased anti-DNA antibodies. In both families we identify biallelic mutations in DNASE2, associated with a loss of DNase II endonuclease activity. We record increased interferon alpha protein levels using digital ELISA, enhanced interferon signaling by RNA-Seq analysis and constitutive upregulation of phosphorylated STAT1 and STAT3 in patient lymphocytes and monocytes. A hematological disease transcriptomic signature and increased numbers of erythroblasts are recorded in patient peripheral blood, suggesting that interferon might have a particular effect on hematopoiesis. These data define a type I interferonopathy due to DNase II deficiency in humans.
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Mathieu Rodéro, Alessandra Tesser, Eva Bartok, Gillian Rice, Erika Della Mina, et al.. Type I interferon-mediated autoinflammation due to DNase II deficiency. Nature Communications, 2017, 8 (1), pp.2176. ⟨10.1038/s41467-017-01932-3⟩. ⟨pasteur-01768950⟩

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