Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome
<h3>Background</h3><p dir="ltr">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.&...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | , , , , , , , , , , , , , , , , , , , , , , |
| Published: |
2022
|
| Subjects: | |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1864513519164063744 |
|---|---|
| author | Hassan Abolhassani (2287858) |
| author2 | Nils Landegren (621152) Paul Bastard (12967485) Marie Materna (18387156) Mohammadreza Modaresi (18387159) Likun Du (92985) Maribel Aranda-Guillén (18173923) Fabian Sardh (18387162) Fanglei Zuo (3232698) Peng Zhang (2071) Harold Marcotte (35624) Nico Marr (349853) Taushif Khan (691254) Manar Ata (9046473) Fatima Al-Ali (14151237) Remi Pescarmona (18387165) Alexandre Belot (282871) Vivien Béziat (204259) Qian Zhang (49333) Jean-Laurent Casanova (64712) Olle Kämpe (138981) Shen-Ying Zhang (140174) Lennart Hammarström (35623) Qiang Pan-Hammarström (92996) |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author author |
| author_facet | Hassan Abolhassani (2287858) Nils Landegren (621152) Paul Bastard (12967485) Marie Materna (18387156) Mohammadreza Modaresi (18387159) Likun Du (92985) Maribel Aranda-Guillén (18173923) Fabian Sardh (18387162) Fanglei Zuo (3232698) Peng Zhang (2071) Harold Marcotte (35624) Nico Marr (349853) Taushif Khan (691254) Manar Ata (9046473) Fatima Al-Ali (14151237) Remi Pescarmona (18387165) Alexandre Belot (282871) Vivien Béziat (204259) Qian Zhang (49333) Jean-Laurent Casanova (64712) Olle Kämpe (138981) Shen-Ying Zhang (140174) Lennart Hammarström (35623) Qiang Pan-Hammarström (92996) |
| author_role | author |
| dc.creator.none.fl_str_mv | Hassan Abolhassani (2287858) Nils Landegren (621152) Paul Bastard (12967485) Marie Materna (18387156) Mohammadreza Modaresi (18387159) Likun Du (92985) Maribel Aranda-Guillén (18173923) Fabian Sardh (18387162) Fanglei Zuo (3232698) Peng Zhang (2071) Harold Marcotte (35624) Nico Marr (349853) Taushif Khan (691254) Manar Ata (9046473) Fatima Al-Ali (14151237) Remi Pescarmona (18387165) Alexandre Belot (282871) Vivien Béziat (204259) Qian Zhang (49333) Jean-Laurent Casanova (64712) Olle Kämpe (138981) Shen-Ying Zhang (140174) Lennart Hammarström (35623) Qiang Pan-Hammarström (92996) |
| dc.date.none.fl_str_mv | 2022-01-28T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1007/s10875-022-01215-7 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Inherited_IFNAR1_Deficiency_in_a_Child_with_Both_Critical_COVID-19_Pneumonia_and_Multisystem_Inflammatory_Syndrome/25611654 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Immunology COVID-19 critical pneumonia multisystem inflammatory syndrome in children (MIS-C) inborn errors of immunity (IEI) primary immunodeficiency (PID) IFNAR1 |
| dc.title.none.fl_str_mv | Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Background</h3><p dir="ltr">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.</p><h3>Objectives</h3><p dir="ltr">To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C.</p><h3>Methods</h3><p dir="ltr">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.</p><h3>Results</h3><p dir="ltr">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.</p><h3>Conclusions</h3><p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Clinical Immunology<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s10875-022-01215-7" target="_blank">https://dx.doi.org/10.1007/s10875-022-01215-7</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_c395288497d366d1b8ee7c1de7755f9a |
| identifier_str_mv | 10.1007/s10875-022-01215-7 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25611654 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory SyndromeHassan Abolhassani (2287858)Nils Landegren (621152)Paul Bastard (12967485)Marie Materna (18387156)Mohammadreza Modaresi (18387159)Likun Du (92985)Maribel Aranda-Guillén (18173923)Fabian Sardh (18387162)Fanglei Zuo (3232698)Peng Zhang (2071)Harold Marcotte (35624)Nico Marr (349853)Taushif Khan (691254)Manar Ata (9046473)Fatima Al-Ali (14151237)Remi Pescarmona (18387165)Alexandre Belot (282871)Vivien Béziat (204259)Qian Zhang (49333)Jean-Laurent Casanova (64712)Olle Kämpe (138981)Shen-Ying Zhang (140174)Lennart Hammarström (35623)Qiang Pan-Hammarström (92996)Biomedical and clinical sciencesImmunologyCOVID-19critical pneumoniamultisystem inflammatory syndrome in children (MIS-C)inborn errors of immunity (IEI)primary immunodeficiency (PID)IFNAR1<h3>Background</h3><p dir="ltr">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.</p><h3>Objectives</h3><p dir="ltr">To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C.</p><h3>Methods</h3><p dir="ltr">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.</p><h3>Results</h3><p dir="ltr">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.</p><h3>Conclusions</h3><p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Clinical Immunology<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s10875-022-01215-7" target="_blank">https://dx.doi.org/10.1007/s10875-022-01215-7</a></p>2022-01-28T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s10875-022-01215-7https://figshare.com/articles/journal_contribution/Inherited_IFNAR1_Deficiency_in_a_Child_with_Both_Critical_COVID-19_Pneumonia_and_Multisystem_Inflammatory_Syndrome/25611654CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/256116542022-01-28T03:00:00Z |
| spellingShingle | Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome Hassan Abolhassani (2287858) Biomedical and clinical sciences Immunology COVID-19 critical pneumonia multisystem inflammatory syndrome in children (MIS-C) inborn errors of immunity (IEI) primary immunodeficiency (PID) IFNAR1 |
| status_str | publishedVersion |
| title | Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome |
| title_full | Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome |
| title_fullStr | Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome |
| title_full_unstemmed | Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome |
| title_short | Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome |
| title_sort | Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome |
| topic | Biomedical and clinical sciences Immunology COVID-19 critical pneumonia multisystem inflammatory syndrome in children (MIS-C) inborn errors of immunity (IEI) primary immunodeficiency (PID) IFNAR1 |