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

Mathieu P. Rodero; Jérémie Decalf; Vincent Bondet; David Hunt; Gillian I. Rice; Scott Werneke; Sarah L. Mcglasson; Marie Alyanakian; Brigitte Bader-Meunier; Christine Barnerias; Nathalia Bellon; Alexandre Belot; Christine Bodemer; Tracy A Briggs; Isabelle Desguerre; Marie Frémond; Marie Hully; Arn M J M Van den Maagdenberg; Isabelle Melki; Isabelle Meyts; Lucile Musset; Nadine Pelzer; Pierre Quartier; Gisela M Terwindt; Joanna Wardlaw; Stewart Wiseman; Frédéric Rieux-Laucat; Yoann Rose; Bénédicte Neven; Christina Hertel; Adrian Hayday; Matthew L. Albert; Flore Rozenberg; Yanick J Crow; Darragh Duffy

doi:10.1084/jem.20161451

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.

Type de document :

Article dans une revue

Journal of Experimental Medicine, Rockefeller University Press, 2017, 214 (5), pp.1547-1555. 〈10.1084/jem.20161451〉

Domaine :

Sciences du Vivant [q-bio] / Immunologie

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Soumis le : mercredi 7 juin 2017 - 12:35:43
Dernière modification le : jeudi 19 avril 2018 - 14:24:03

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