Identification of biomarkers for COVID-19 associated secondary hemophagocytic lymphohistiocytosis.

Autor:	Canny SP; Center for Fundamental Immunology, Benaroya Research Institute, Seattle, WA.; Department of Pediatrics, University of Washington, Seattle, WA., Stanaway IB; Kidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA., Holton SE; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.; Center for Translational Immunology, Benaroya Research Institute, Seattle, WA., Mitchem M; Center for Translational Immunology, Benaroya Research Institute, Seattle, WA., O'Rourke AR; Center for Fundamental Immunology, Benaroya Research Institute, Seattle, WA., Pribitzer S; Center for Systems Immunology, Benaroya Research Institute, Seattle, WA., Baxter SK; Department of Pediatrics, University of Washington, Seattle, WA.; Sonoma Biotherapeutics, Seattle, WA., Wurfel MM; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA., Malhotra U; Department of Infectious Disease, Virginia Mason Medical Center, Seattle, WA.; Department of Medicine, Section of Infectious Diseases, University of Washington, Seattle, WA., Buckner JH; Center for Translational Immunology, Benaroya Research Institute, Seattle, WA.; Department of Immunology, University of Washington, Seattle, WA., Bhatraju PK; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA., Morrell ED; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA., Speake C; Center for Interventional Immunology, Benaroya Research Institute, Seattle, WA., Mikacenic C; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.; Center for Translational Immunology, Benaroya Research Institute, Seattle, WA., Hamerman JA; Center for Fundamental Immunology, Benaroya Research Institute, Seattle, WA.; Department of Immunology, University of Washington, Seattle, WA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Aug 15. Date of Electronic Publication: 2024 Aug 15.
DOI:	10.1101/2024.08.13.607855
Abstrakt:	Objectives: We aimed to define and validate novel biomarkers that could identify individuals with COVID-19 associated secondary hemophagocytic lymphohistiocytosis (sHLH) and to test whether fatalities due to COVID-19 in the presence of sHLH were associated with specific defects in the immune system. Design: In two cohorts of adult patients presenting with COVID-19 in 2020 and 2021, clinical lab values and serum proteomics were assessed. Subjects identified as having sHLH were compared to those with COVID-19 without sHLH. Eight deceased patients defined as COVID-sHLH underwent genomic sequencing in order to identify variants in immune-related genes. Setting: Two tertiary care hospitals in Seattle, Washington (Virginia Mason Medical Center and Harborview Medical Center). Patients: 186 patients with COVID-19. Interventions: None. Measurements and Main Results: Nine percent of enrolled COVID-19 subjects met our defined criteria for sHLH. Using broad serum proteomic approaches (O-link and SomaScan), we identified three biomarkers for COVID-19 associated sHLH (soluble PD-L1, TNF-R1, and IL-18BP), supporting a role for proteins previously associated with other forms of sHLH (IL-18BP and sTNF-R1). We also identified novel biomarkers and pathways of COVID-sHLH, including sPD-L1 and the syntaxin pathway. We detected variants in several genes involved in immune responses in individuals with COVID-sHLH, including in DOCK8 and in TMPRSS15 , suggesting that genetic alterations in immune-related genes may contribute to hyperinflammation and fatal outcomes in COVID-19. Conclusions: Biomarkers of COVID-19 associated sHLH, such as soluble PD-L1, and pathways, such as the syntaxin pathway, and variants in immune genes in these individuals, suggest critical roles for the immune response in driving sHLH in the context of COVID-19.
Databáze:	MEDLINE
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