Differential levels of IFNα subtypes in autoimmunity and viral infection

Research output: Contribution to journalArticlepeer-review

Authors

  • Vincent Bondet
  • Mathieu P. Rodero
  • Céline Posseme
  • Pierre Bost
  • Jérémie Decalf
  • Liis Haljasmägi
  • Nassima Bekaddour
  • Gillian I. Rice
  • Vinit Upasani
  • Jean Philippe Herbeuval
  • Tracy A. Briggs
  • Ian N. Bruce
  • Claudia Mauri
  • David Isenberg
  • Madhvi Menon
  • David Hunt
  • Benno Schwikowski
  • Xavier Mariette
  • Stanislas Pol
  • Flore Rozenberg
  • Tineke Cantaert
  • J. Eric Gottenberg
  • Kai Kisand
  • Darragh Duffy

Colleges, School and Institutes

External organisations

  • Institut Pasteur
  • Université Paris Descartes
  • Laboratoire Kastler Brossel, ENS, UPMC-Paris 6
  • University of Tartu
  • University of Manchester
  • Institut Pasteur du Cambodge
  • Sandwell and West Birmingham Hospitals NHS Trust
  • University College London
  • University of Edinburgh
  • Paris-Saclay University
  • Hôpital Cochin
  • IN2P3
  • Manchester University Hospitals NHS Foundation Trust

Abstract

Type I interferons are essential for host response to viral infections, while dysregulation of their response can result in autoinflammation or autoimmunity. Among IFNα (alpha) responses, 13 subtypes exist that signal through the same receptor, but have been reported to have different effector functions. However, the lack of available tools for discriminating these closely related subtypes, in particular at the protein level, has restricted the study of their differential roles in disease. We developed a digital ELISA with specificity and high sensitivity for the IFNα2 subtype. Application of this assay, in parallel with our previously described pan-IFNα assay, allowed us to study different IFNα protein responses following cellular stimulation and in diverse patient cohorts. We observed different ratios of IFNα protein responses between viral infection and autoimmune patients. This analysis also revealed a small percentage of autoimmune patients with high IFNα2 protein measurements but low pan-IFNα measurements. Correlation with an ISG score and functional activity showed that in this small sub group of patients, IFNα2 protein measurements did not reflect its biological activity. This unusual phenotype was partly explained by the presence of anti-IFNα auto-antibodies in a subset of autoimmune patients. This study reports ultrasensitive assays for the study of IFNα proteins in patient samples and highlights the insights that can be obtained from the use of multiple phenotypic readouts in translational and clinical studies.

Bibliographic note

Funding Information: We thank all patients and healthy donors who provided samples used in this study, as well as the clinical support teams that enabled their collection. We thank Immunoqure for provision of mAbs for the pan-IFNα assay. We acknowledge support from the ANR (CE17001002) awarded to DD. Publisher Copyright: © 2021 The Author(s)

Details

Original languageEnglish
Article number155533
Number of pages12
JournalCytokine
Volume144
Early online date30 Apr 2021
Publication statusPublished - Aug 2021

Keywords

  • Anti-IFNα autoantibodies, Autoimmunity, IFN function, IFNα subtypes, TLR activation, Viral infection