Hemophagocytic Lymphohistiocytosis Gene Variants in Multisystem Inflammatory Syndrome in Children
Multisystem inflammatory syndrome in children (MIS-C) affects few children previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In 2020, 45 children admitted to our hospital for MIS-C underwent genetic screening with a commercial 109-immune-gene panel. Thirty-nine c...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/11/3/417 |
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| author | Anshul Vagrecha Mingce Zhang Suchitra Acharya Shannon Lozinsky Aaron Singer Chana Levine Maha Al-Ghafry Carolyn Fein Levy Randy Q. Cron |
| author_facet | Anshul Vagrecha Mingce Zhang Suchitra Acharya Shannon Lozinsky Aaron Singer Chana Levine Maha Al-Ghafry Carolyn Fein Levy Randy Q. Cron |
| author_sort | Anshul Vagrecha |
| collection | DOAJ |
| description | Multisystem inflammatory syndrome in children (MIS-C) affects few children previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In 2020, 45 children admitted to our hospital for MIS-C underwent genetic screening with a commercial 109-immune-gene panel. Thirty-nine children were diagnosed with MIS-C, and 25.4% of the 39 MIS-C patients harbored rare heterozygous missense mutations either in primary hemophagocytic lymphohistiocytosis (pHLH) genes (LYST, STXBP2, PRF1, UNC13D, AP3B1) or the HLH-associated gene DOCK8 (four variants). We demonstrate that foamy virus introduction of cDNA for the four DOCK8 variants into human NK-92 natural killer (NK) cells led to decreased CD107a expression (degranulation) and decreased NK cell lytic function in vitro for each variant. Heterozygous carriers of missense mutations in pHLH genes and DOCK8 may serve as risk factors for development of MIS-C among children previously infected with SARS-CoV-2. |
| first_indexed | 2024-03-09T13:50:23Z |
| format | Article |
| id | doaj.art-b19da3dbd46c49bda45704cbad562c86 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T13:50:23Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-b19da3dbd46c49bda45704cbad562c862023-11-30T20:51:54ZengMDPI AGBiology2079-77372022-03-0111341710.3390/biology11030417Hemophagocytic Lymphohistiocytosis Gene Variants in Multisystem Inflammatory Syndrome in ChildrenAnshul Vagrecha0Mingce Zhang1Suchitra Acharya2Shannon Lozinsky3Aaron Singer4Chana Levine5Maha Al-Ghafry6Carolyn Fein Levy7Randy Q. Cron8Department of Pediatrics, Division of Hematology/Oncology and Cellular Therapy, Cohen Children’s Medical Center, New Hyde Park, NY 11040, USADivision of Pediatric Rheumatology, Children’s of Alabama, University of Alabama at Birmingham, Birmingham, AL 35233, USADepartment of Pediatrics, Division of Hematology/Oncology and Cellular Therapy, Cohen Children’s Medical Center, New Hyde Park, NY 11040, USADepartment of Pediatrics, Division of Hematology/Oncology and Cellular Therapy, Cohen Children’s Medical Center, New Hyde Park, NY 11040, USAYeshiva College, Yeshiva University, New York, NY 10033, USADepartment of Pediatrics, Division of Hematology/Oncology and Cellular Therapy, Cohen Children’s Medical Center, New Hyde Park, NY 11040, USADepartment of Pediatrics, Division of Hematology/Oncology and Cellular Therapy, Cohen Children’s Medical Center, New Hyde Park, NY 11040, USADepartment of Pediatrics, Division of Hematology/Oncology and Cellular Therapy, Cohen Children’s Medical Center, New Hyde Park, NY 11040, USADivision of Pediatric Rheumatology, Children’s of Alabama, University of Alabama at Birmingham, Birmingham, AL 35233, USAMultisystem inflammatory syndrome in children (MIS-C) affects few children previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In 2020, 45 children admitted to our hospital for MIS-C underwent genetic screening with a commercial 109-immune-gene panel. Thirty-nine children were diagnosed with MIS-C, and 25.4% of the 39 MIS-C patients harbored rare heterozygous missense mutations either in primary hemophagocytic lymphohistiocytosis (pHLH) genes (LYST, STXBP2, PRF1, UNC13D, AP3B1) or the HLH-associated gene DOCK8 (four variants). We demonstrate that foamy virus introduction of cDNA for the four DOCK8 variants into human NK-92 natural killer (NK) cells led to decreased CD107a expression (degranulation) and decreased NK cell lytic function in vitro for each variant. Heterozygous carriers of missense mutations in pHLH genes and DOCK8 may serve as risk factors for development of MIS-C among children previously infected with SARS-CoV-2.https://www.mdpi.com/2079-7737/11/3/417MIS-CHLHVUSDOCK8 |
| spellingShingle | Anshul Vagrecha Mingce Zhang Suchitra Acharya Shannon Lozinsky Aaron Singer Chana Levine Maha Al-Ghafry Carolyn Fein Levy Randy Q. Cron Hemophagocytic Lymphohistiocytosis Gene Variants in Multisystem Inflammatory Syndrome in Children Biology MIS-C HLH VUS DOCK8 |
| title | Hemophagocytic Lymphohistiocytosis Gene Variants in Multisystem Inflammatory Syndrome in Children |
| title_full | Hemophagocytic Lymphohistiocytosis Gene Variants in Multisystem Inflammatory Syndrome in Children |
| title_fullStr | Hemophagocytic Lymphohistiocytosis Gene Variants in Multisystem Inflammatory Syndrome in Children |
| title_full_unstemmed | Hemophagocytic Lymphohistiocytosis Gene Variants in Multisystem Inflammatory Syndrome in Children |
| title_short | Hemophagocytic Lymphohistiocytosis Gene Variants in Multisystem Inflammatory Syndrome in Children |
| title_sort | hemophagocytic lymphohistiocytosis gene variants in multisystem inflammatory syndrome in children |
| topic | MIS-C HLH VUS DOCK8 |
| url | https://www.mdpi.com/2079-7737/11/3/417 |
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