Type I interferon-mediated autoinflammation due to DNase II deficiency - Institut Pasteur Access content directly
Journal Articles Nature Communications Year : 2017

Type I interferon-mediated autoinflammation due to DNase II deficiency

Type I interferon-mediated autoinflammation due to DNase II deficiency.

Gillian Rice
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  • PersonId : 932509
Erika Della Mina
Marine M Depp
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Darragh Duffy
Marie-Louise Frémond
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Flavia Guillem
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  • PersonId : 932298
Luis Seabra
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  • PersonId : 955942
Carolina Uggenti
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Stefano Volpi
Sophie Candon
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Roberta Caorsi
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Monique Fabre
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Flavio Faletra
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Muriel Girard
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Annie Harroche
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Evelyn Hartmann
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Annalisa Marcuzzi
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Tiffany Pascreau
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Serena Pastore
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Capucine Picard
Paolo Picco
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Elisa Piscianz
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Marion Rabant
Andrea Taddio
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Florence Uettwiller
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Erica Valencic
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Diego Vozzi
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Winfried Barchet
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Olivier Hermine


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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Dates and versions

pasteur-01768950 , version 1 (17-04-2018)





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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