IFNAR2 Deficiency Causing Dysregulation of NK Cell Functions and Presenting With Hemophagocytic Lymphohistiocytosis

Chiara Passarelli, Adele Civino, Marianna N. Rossi, Loredana Cifaldi, Valentina Lanari, Gian Marco Moneta, Ivan Caiello, Claudia Bracaglia, Raffaele Montinaro, Antonio Novelli, Fabrizio De Benedetti, Giusi Prencipe

Research output: Contribution to journalArticlepeer-review


We describe a 2 year old boy with two previously undescribed frameshift mutations in the interferon (IFN)α/β receptor 2 (IFNAR2) gene presenting with hemophagocytic lymphohistiocytosis (HLH) following measles-mumps-rubella vaccination. Functional analyses show the absence of response to type I IFN in the patient’s cells, as revealed by the lack of phosphorylation of STAT1 and the lack of induction of interferon-stimulated genes upon ex vivo stimulation with IFNα. HLH has been reported in patients with inborn errors of type I IFN-mediated immune responses following vaccination with live-attenuated viruses. The relation between HLH and defective type I IFN-mediated responses is unclear. We show that in patient’s natural killer (NK) cells stimulated with IFNα the expected increase in degranulation and inhibition of IFNγ production were affected. These data support a role for NK cell function dysregulation and lack of inhibition of IFNγ production as contributors to the development of HLH in patients with impaired type I IFN signaling.

Original languageEnglish
Article number937
JournalFrontiers in Genetics
Publication statusPublished - Sep 18 2020


  • clinical exome
  • hemophagocityc lymphohistiocytosis
  • IFNAR2
  • interferon
  • NK cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)


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