Detection of interferon alpha protein reveals differential levels and cellular sources in disease.

Mathieu P. Rodero 1 Jérémie Decalf 2 Vincent Bondet 2 David Hunt 3, 4 Gillian I. Rice 5 Scott Werneke 2 Sarah L. Mcglasson 4, 3 Marie Alyanakian 6 Brigitte Bader-Meunier 7, 8 Christine Barnerias 9 Nathalia Bellon 10 Alexandre Belot 11 Christine Bodemer 10, 12 Tracy A Briggs 5, 13 Isabelle Desguerre 9 Marie Frémond 1 Marie Hully 9 Arn M J M Van den Maagdenberg 14, 15 Isabelle Melki 1, 16, 17 Isabelle Meyts 18, 19 Lucile Musset 20 Nadine Pelzer 14 Pierre Quartier 16 Gisela M Terwindt 14 Joanna Wardlaw 3 Stewart Wiseman 3 Frédéric Rieux-Laucat 12, 8 Yoann Rose 1 Bénédicte Neven 7 Christina Hertel 21 Adrian Hayday 22, 23 Matthew L. Albert 2 Flore Rozenberg 24, 25 Yanick J Crow 1, 26, * Darragh Duffy 2, *
* Auteur correspondant
1 Laboratory of Neurogenetics and Neuroinflammation
2 Immunobiologie des Cellules dendritiques
3 CCBS - Centre For Clinical Brain Sciences - Neuroimaging Sciences [Edinburgh, U.K.]
4 Medical Research Council (MRC) Human Genetics Unit [Edinburgh]
5 Division of Evolution and Genomic Science [Manchester]
6 Laboratoire d’Immunologie Biologique [Necker]
7 Unité d’immunologie, d’hématologie et de rhumatologie pédiatriques [Hôpital Necker]
8 Laboratory of Immunogenetics of Pediatric Autoimmunity [Paris]
9 Service de neurologie pédiatrique [CHU Necker]
10 Service de dermatologie [CHU Necker-Enfants malades]
11 Department of Paediatric Rheumatology [Lyon]
12 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
13 Manchester Centre for Genomic Medicine
14 Department of Neurology
15 Departments of Human Genetics & Neurology
16 Service d'immunologie, hématologie et rhumatologie pédiatriques [CHU Necker]
17 General Paediatrics, Infectious Disease and Internal Medicine Department [Robert-Debré]
18 Department of Microbiology and Immunology
19 Pediatric Immunodeficiencies
20 Service d'immunologie [CHU Pitié-Salpétrière]
21 ImmunoQure AG
22 Peter Gorer Department of Immunobiology
23 The Francis Crick Institute
24 UPD5 - Université Paris Descartes - Paris 5
25 Service de Virologie [CHU Cochin]
26 Département de Génétique [Necker]
Abstract : Type I interferons (IFNs) are essential mediators of antiviral responses. These cytokines have been implicated in the pathogenesis of autoimmunity, most notably systemic lupus erythematosus (SLE), diabetes mellitus, and dermatomyositis, as well as monogenic type I interferonopathies. Despite a fundamental role in health and disease, the direct quantification of type I IFNs has been challenging. Using single-molecule array (Simoa) digital ELISA technology, we recorded attomolar concentrations of IFNα in healthy donors, viral infection, and complex and monogenic interferonopathies. IFNα protein correlated well with functional activity and IFN-stimulated gene expression. High circulating IFNα levels were associated with increased clinical severity in SLE patients, and a study of the cellular source of IFNα protein indicated disease-specific mechanisms. Measurement of IFNα attomolar concentrations by digital ELISA will enhance our understanding of IFN biology and potentially improve the diagnosis and stratification of pathologies associated with IFN dysregulation.
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Journal of Experimental Medicine, Rockefeller University Press, 2017, 214 (5), pp.1547-1555. 〈10.1084/jem.20161451〉
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Mathieu P. Rodero, Jérémie Decalf, Vincent Bondet, David Hunt, Gillian I. Rice, et al.. Detection of interferon alpha protein reveals differential levels and cellular sources in disease.. Journal of Experimental Medicine, Rockefeller University Press, 2017, 214 (5), pp.1547-1555. 〈10.1084/jem.20161451〉. 〈pasteur-01534181〉

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