IFNAR2 Deficiency Causing Dysregulation of NK Cell Functions and Presenting With Hemophagocytic Lymphohistiocytosis
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 i...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2020.00937/full |
| _version_ | 1818191127566614528 |
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| author | Chiara Passarelli Adele Civino Marianna N. Rossi Loredana Cifaldi Loredana Cifaldi Valentina Lanari Gian Marco Moneta Ivan Caiello Claudia Bracaglia Raffaele Montinaro Antonio Novelli Fabrizio De Benedetti Giusi Prencipe |
| author_facet | Chiara Passarelli Adele Civino Marianna N. Rossi Loredana Cifaldi Loredana Cifaldi Valentina Lanari Gian Marco Moneta Ivan Caiello Claudia Bracaglia Raffaele Montinaro Antonio Novelli Fabrizio De Benedetti Giusi Prencipe |
| author_sort | Chiara Passarelli |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T00:09:40Z |
| format | Article |
| id | doaj.art-bb5fea9493f8406b8f8bc61a49ee24a1 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-12T00:09:40Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-bb5fea9493f8406b8f8bc61a49ee24a12022-12-22T00:45:00ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-09-011110.3389/fgene.2020.00937555244IFNAR2 Deficiency Causing Dysregulation of NK Cell Functions and Presenting With Hemophagocytic LymphohistiocytosisChiara Passarelli0Adele Civino1Marianna N. Rossi2Loredana Cifaldi3Loredana Cifaldi4Valentina Lanari5Gian Marco Moneta6Ivan Caiello7Claudia Bracaglia8Raffaele Montinaro9Antonio Novelli10Fabrizio De Benedetti11Giusi Prencipe12U.O.C. Laboratory of Medical Genetics, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyRheumatology and Paediatric Immunology, PO “Vito Fazzi,” Lecce, ItalyDivision of Rheumatology, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyAcademic Department of Pediatrics (DPUO), Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDepartment of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Rome, ItalyU.O.C. Laboratory of Medical Genetics, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDivision of Rheumatology, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDivision of Rheumatology, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDivision of Rheumatology, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDivision of Pediatrics, PO “Santa Caterina Novella,” Galatina, ItalyU.O.C. Laboratory of Medical Genetics, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDivision of Rheumatology, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDivision of Rheumatology, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyWe 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.https://www.frontiersin.org/article/10.3389/fgene.2020.00937/fullhemophagocityc lymphohistiocytosisinterferonIFNAR2NK cellsclinical exome |
| spellingShingle | Chiara Passarelli Adele Civino Marianna N. Rossi Loredana Cifaldi Loredana Cifaldi Valentina Lanari Gian Marco Moneta Ivan Caiello Claudia Bracaglia Raffaele Montinaro Antonio Novelli Fabrizio De Benedetti Giusi Prencipe IFNAR2 Deficiency Causing Dysregulation of NK Cell Functions and Presenting With Hemophagocytic Lymphohistiocytosis Frontiers in Genetics hemophagocityc lymphohistiocytosis interferon IFNAR2 NK cells clinical exome |
| title | IFNAR2 Deficiency Causing Dysregulation of NK Cell Functions and Presenting With Hemophagocytic Lymphohistiocytosis |
| title_full | IFNAR2 Deficiency Causing Dysregulation of NK Cell Functions and Presenting With Hemophagocytic Lymphohistiocytosis |
| title_fullStr | IFNAR2 Deficiency Causing Dysregulation of NK Cell Functions and Presenting With Hemophagocytic Lymphohistiocytosis |
| title_full_unstemmed | IFNAR2 Deficiency Causing Dysregulation of NK Cell Functions and Presenting With Hemophagocytic Lymphohistiocytosis |
| title_short | IFNAR2 Deficiency Causing Dysregulation of NK Cell Functions and Presenting With Hemophagocytic Lymphohistiocytosis |
| title_sort | ifnar2 deficiency causing dysregulation of nk cell functions and presenting with hemophagocytic lymphohistiocytosis |
| topic | hemophagocityc lymphohistiocytosis interferon IFNAR2 NK cells clinical exome |
| url | https://www.frontiersin.org/article/10.3389/fgene.2020.00937/full |
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