Differential levels of IFNα subtypes in autoimmunity and viral infection

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Vincent Bondet
  • Mathieu P Rodero
  • Céline Posseme
  • Pierre Bost
  • Jérémie Decalf
  • Liis Haljasmägi
  • Nassima Bekaddour
  • Vinit Upasani
  • Jean-Philippe Herbeuval
  • Claudia Mauri
  • David Isenberg
  • David Hunt
  • Benno Schwikowski
  • Xavier Mariette
  • Stanislas Pol
  • Flore Rozenberg
  • Tineke Cantaert
  • J Eric Gottenberg
  • Kai Kisand
  • Darragh Duffy

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.

Bibliographical metadata

Original languageEnglish
Article number155533
JournalCytokine
Volume144
Early online date30 Apr 2021
DOIs
Publication statusPublished - 1 Aug 2021