Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome
© 2022. The Author(s)..
BACKGROUND: Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem inflammatory syndrome in children (MIS-C) remain elusive.
OBJECTIVES: To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C.
METHODS: Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured.
RESULTS: We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in IFNAR1, underlying autosomal recessive IFNAR1 deficiency.
CONCLUSIONS: Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
Journal of clinical immunology - 42(2022), 3 vom: 29. Apr., Seite 471-483 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Abolhassani, Hassan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.04.2022 Date Revised 16.07.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s10875-022-01215-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Abolhassani, Hassan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 20.04.2022 | ||
| 500 | |a Date Revised 16.07.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a BACKGROUND: Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem inflammatory syndrome in children (MIS-C) remain elusive | ||
| 520 | |a OBJECTIVES: To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C | ||
| 520 | |a METHODS: Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured | ||
| 520 | |a RESULTS: We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in IFNAR1, underlying autosomal recessive IFNAR1 deficiency | ||
| 520 | |a CONCLUSIONS: Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients | ||
| 650 | 4 | |a Case Reports | |
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| 650 | 4 | |a critical pneumonia | |
| 650 | 4 | |a inborn errors of immunity (IEI) | |
| 650 | 4 | |a multisystem inflammatory syndrome in children (MIS-C) | |
| 650 | 4 | |a primary immunodeficiency (PID) | |
| 650 | 7 | |a Autoantibodies |2 NLM | |
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| 700 | 1 | |a Du, Likun |e verfasserin |4 aut | |
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| 700 | 1 | |a Zuo, Fanglei |e verfasserin |4 aut | |
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| 700 | 1 | |a Pescarmona, Remi |e verfasserin |4 aut | |
| 700 | 1 | |a Belot, Alexandre |e verfasserin |4 aut | |
| 700 | 1 | |a Béziat, Vivien |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Casanova, Jean-Laurent |e verfasserin |4 aut | |
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