Detection of interferon alpha protein reveals differential levels and cellular sources in disease-Reference-Cited by-同舟云学术

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

Published:2017-04-18 Issue:5 Volume:214 Page:1547-1555
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
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Author:

Rodero Mathieu P.¹,Decalf Jérémie²³^ORCID,Bondet Vincent²³^ORCID,Hunt David⁴⁵^ORCID,Rice Gillian I.⁶,Werneke Scott²³,McGlasson Sarah L.⁴⁵^ORCID,Alyanakian Marie-Alexandra⁷,Bader-Meunier Brigitte⁸⁹^ORCID,Barnerias Christine¹⁰,Bellon Nathalia¹¹,Belot Alexandre¹²,Bodemer Christine¹³¹¹,Briggs Tracy A.⁶¹⁴^ORCID,Desguerre Isabelle¹⁰,Frémond Marie-Louise¹^ORCID,Hully Marie¹⁰^ORCID,van den Maagdenberg Arn M.J.M.¹⁵¹⁶^ORCID,Melki Isabelle¹⁸¹⁷^ORCID,Meyts Isabelle¹⁸¹⁹,Musset Lucile²⁰,Pelzer Nadine¹⁵^ORCID,Quartier Pierre¹³⁸^ORCID,Terwindt Gisela M.¹⁵^ORCID,Wardlaw Joanna⁵,Wiseman Stewart⁵,Rieux-Laucat Frédéric¹³⁹^ORCID,Rose Yoann¹,Neven Bénédicte¹³⁸⁹,Hertel Christina²¹,Hayday Adrian²²²³,Albert Matthew L.²²⁴³,Rozenberg Flore²⁵,Crow Yanick J.¹¹³⁶²⁶^ORCID,Duffy Darragh²²⁴³^ORCID

Affiliation:

1. Laboratory of Neurogenetics and Neuroinflammation, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1163, Institut Imagine, 75015 Paris, France

2. Immunobiology of Dendritic Cells, Institut Pasteur, 75015 Paris, France

3. INSERM U1223, 75015 Paris, France

4. Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH8 9YL, Scotland, UK

5. Centre for Clinical Brain Sciences (CCBS), University of Edinburgh, Edinburgh EH8 9YL, Scotland, UK

6. Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9NT, England, UK

7. Laboratoire d’Immunologie Biologique, Assistance Publique–Hôpitaux de Paris, Hôpital Universitaire Necker-Enfants Malades, 75015 Paris, France

8. Pediatric Immunology-Hematology and Rheumatology Unit, Assistance Publique–Hôpitaux de Paris, Hôpital Universitaire Necker-Enfants Malades, 75015 Paris, France

9. Laboratory of Immunogenetics of Pediatric Autoimmunity, INSERM UMR 1163, 75015 Paris, France

10. Department of Paediatric Neurology, Assistance Publique–Hôpitaux de Paris, Hôpital Universitaire Necker-Enfants Malades, 75015 Paris, France

11. Department of Paediatric Dermatology, Reference Centre for Rare Skin Disorders (MAGEC), Assistance Publique–Hôpitaux de Paris, Hôpital Universitaire Necker-Enfants Malades, 75015 Paris, France

12. Department of Paediatric Rheumatology, Hospices Civils de Lyon, INSERM U1111, 69007 Lyon, France

13. Université Paris Descartes, Université Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France

14. Manchester Centre for Genomic Medicine, St Mary’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9NT, England, UK

15. Department of Neurology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

16. Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

17. General Paediatrics, Infectious Disease and Internal Medicine Department, Assistance Publique–Hôpitaux de Paris, Robert-Debré Hospital, 75019 Paris, France

18. Department of Pediatrics, University Hospitals Leuven, 3000 Leuven, Belgium

19. Department of Microbiology and Immunology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium

20. Department of Immunology, Assistance Publique–Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, 75013 Paris, France

21. ImmunoQure AG, 42012 Düsseldorf, Germany

22. Peter Gorer Department of Immunobiology, King’s College, Guy’s Hospital, London SE1 9RT, England, UK

23. Francis Crick Institute, London NW1 1BF, England, UK

24. Centre for Translational Research, Institut Pasteur, 75015 Paris, France

25. Service de Virologie, Université Paris Descartes, Université Sorbonne Paris Cité, Assistance–Publique Hôpitaux de Paris, Groupe Hospitalier Universitaire Paris Centre, 75014 Paris, France

26. Département de Génétique, Assistance Publique–Hôpitaux de Paris, Hôpital Universitaire Necker-Enfants Malades, 75015 Paris, France

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.

Funder

European Research Council

European Leukodystrophy Association

Agence Nationale de la Recherche

ANR

EU FP7

PasteurInnov

Lupus UK

Wellcome Trust

Publisher

Rockefeller University Press

Subject