Activating Killer-Cell Immunoglobulin-Like Receptors Are Associated With the Severity of Coronavirus Disease 2019
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- Enrique Bernal
- Infectious Disease Unit, Reina Sofia University Hospital and the Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain
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- Lourdes Gimeno
- Immunology Service, Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA) and Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain
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- María J Alcaraz
- Infectious Disease Unit, Reina Sofia University Hospital and the Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain
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- Ahmed A Quadeer
- Department of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Hong Kong, China
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- Marta Moreno
- Internal Medicine Service, Hospital Universitario Morales Meseguer, Murcia, Spain
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- María V Martínez-Sánchez
- Immunology Service, Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA) and Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain
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- José A Campillo
- Immunology Service, Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA) and Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain
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- Jose M Gomez
- Internal Medicine Service, Hospital Universitario Morales Meseguer, Murcia, Spain
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- Ana Pelaez
- Internal Medicine Service, Hospital Rafael Méndez, Lorca, Spain
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- Elisa García
- Infectious Disesase Unit, Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA) and Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain
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- Maite Herranz
- Internal Medicine Service, Hospital Universitario Morales Meseguer, Murcia, Spain
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- Marta Hernández-Olivo
- Pheumology Service, Hospital Universitario Santa Lucía, Murcia, Spain
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- Elisa Martínez-Alfaro
- Internal Medicine Service, Hospital General de Albacete, Albacete, Spain
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- Antonia Alcaraz
- Infectious Disease Unit, Reina Sofia University Hospital and the Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain
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- Ángeles Muñoz
- Infectious Disease Unit, Reina Sofia University Hospital and the Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain
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- Alfredo Cano
- Infectious Disease Unit, Reina Sofia University Hospital and the Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain
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- Matthew R McKay
- Department of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Hong Kong, China
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- Manuel Muro
- Immunology Service, Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA) and Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain
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- Alfredo Minguela
- Immunology Service, Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA) and Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain
Description
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Etiopathogenesis of the clinical variability of the coronavirus disease 2019 (COVID-19) remains mostly unknown. In this study, we investigate the role of killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen class-I (HLA-I) interactions in the susceptibility and severity of COVID-19.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We performed KIR and HLA-I genotyping and natural killer cell (NKc) receptors immunophenotyping in 201 symptomatic patients and 210 noninfected controls.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>The NKcs with a distinctive immunophenotype, suggestive of recent activation (KIR2DS4low CD16low CD226low CD56high TIGIThigh NKG2Ahigh), expanded in patients with severe COVID-19. This was associated with a higher frequency of the functional A-telomeric activating KIR2DS4 in severe versus mild and/or moderate patients and controls (83.7%, 55.7% and 36.2%, P < 7.7 × 10−9). In patients with mild and/or moderate infection, HLA-B*15:01 was associated with higher frequencies of activating B-telomeric KIR3DS1 compared with patients with other HLA-B*15 subtypes and noninfected controls (90.9%, 42.9%, and 47.3%; P < .002; Pc = 0.022). This strongly suggests that HLA-B*15:01 specifically presenting severe acute respiratory syndrome coronavirus 2 peptides could form a neoligand interacting with KIR3DS1. Likewise, a putative neoligand for KIR2DS4 could arise from other HLA-I molecules presenting severe acute respiratory syndrome coronavirus 2 peptides expressed on infected an/or activated lung antigen-presenting cells.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our results support a crucial role of NKcs in the clinical variability of COVID-19 with specific KIR/ligand interactions associated with disease severity.</jats:p> </jats:sec>
Journal
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- The Journal of Infectious Diseases
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The Journal of Infectious Diseases 224 (2), 229-240, 2021-04-30
Oxford University Press (OUP)
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Details 詳細情報について
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- CRID
- 1360017285993960448
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- ISSN
- 15376613
- 00221899
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- Data Source
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- Crossref