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 ^{6, 7} Christine Barnerias ⁸ Nathalia Bellon ⁹ Alexandre Belot ^{10, 11} Christine Bodemer ^{9, 7} Tracy A Briggs ^{5, 12} Isabelle Desguerre ⁸ Marie Frémond ¹ Marie Hully ⁸ Arn M J M Van den Maagdenberg ^{13, 14} Isabelle Melki ^{1, 6, 15} Isabelle Meyts ^{16, 17} Lucile Musset ¹⁸ Nadine Pelzer ¹³ Pierre Quartier ⁶ Gisela M Terwindt ¹³ Joanna Wardlaw ³ Stewart Wiseman ³ Frédéric Rieux-Laucat ⁷ Yoann Rose ¹ Bénédicte Neven ⁶ Christina Hertel ¹⁹ Adrian Hayday ^{20, 21} Matthew L. Albert ² Flore Rozenberg ^{22, 23} Yanick J Crow ^{1, 24, *} Darragh Duffy ^{2, *}

* Auteur correspondant

1 Equipe Inserm U1163 - Laboratory of neurogenetics and neuroinflammation

IMAGINE - U1163 - Imagine - Institut des maladies génétiques

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 Service d'immuno-hématologie pédiatrique [CHU Necker]

7 IMAGINE - U1163 - Imagine - Institut des maladies génétiques

8 Service de neurologie pédiatrique [CHU Necker]

9 Service de dermatologie [CHU Necker]

10 CIRI - Centre International de Recherche en Infectiologie

11 HCL - Hospices Civils de Lyon

12 Manchester Centre for Genomic Medicine

13 Department of Neurology

14 Departments of Human Genetics & Neurology

15 General Paediatrics, Infectious Disease and Internal Medicine Department [Robert-Debré]

16 Department of Microbiology and Immunology

17 Pediatric Immunodeficiencies

18 Service d'immunologie [CHU Pitié-Salpétrière]

19 ImmunoQure AG

20 Peter Gorer Department of Immunobiology

21 The Francis Crick Institute

22 UPD5 - Université Paris Descartes - Paris 5

23 Service de Virologie [CHU Cochin]

24 Service de Génétique Médicale [CHU 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 : vendredi 9 novembre 2018 - 16:52:02

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