The Journal of allergy and clinical immunology · 2024
Features of hyperinflammation link the biology of Epstein-Barr virus infection and cytokine storm syndromes.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Liu Meng, Brodeur Kailey E, Bledsoe Jacob R, Harris Claudia N, Joerger Jill, Weng Rachel, Hsu Evan E, Lam Michael T, Rimland Casey A, LeSon Courtney E, Yue Jian, Henderson Lauren A, Dedeoglu Fatma, Newburger Jane W, Nigrovic Peter A, Son Mary Beth F, Lee Pui Y
Аннотация
BACKGROUND: Overt immune activation by viral infections can lead to cytokine storm syndromes, such as hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS).
OBJECTIVE: We aimed to compare the immune response to different viral pathogens to understand the connection between infections and cytokine storm syndromes.
METHODS: We recruited children who sought care at the emergency department with fever for ≥3 days. We performed immune profiling using Olink proximity extension assay and flow cytometry. We compared the findings with cases of HLH, MAS, Kawasaki disease (KD), and multisystem inflammatory syndrome in children (MIS-C).
RESULTS: We enrolled 352 febrile patients and studied 110 cases of confirmed common viral infections. We found that Epstein-Barr virus (EBV) uniquely triggered high levels of multiple cytokines (IL-18, IL-27, TNF, FLT3 ligand, and lymphotoxin alpha) and IFN-γ-induced chemokines (CXCL9/10/11 and CCL19). These patterns are similar to the hyperinflammatory response associated with HLH/MAS but are less consistent with the findings in KD and MIS-C. Flow cytometry analysis revealed that CD38+HLA-DR+ T lymphocytes, which are pathogenic cells responsible for IFN-γ production in HLH/MAS, are vastly expanded in patients with acute EBV infection. Cell sorting identified CD38+HLA-DR+ T cells as atypical lymphocytes that are classically associated with acute EBV infection.
CONCLUSION: This work broadens our understanding of common viral infections in children and provides an immunologic basis for the link between EBV infection and HLH/MAS.
OBJECTIVE: We aimed to compare the immune response to different viral pathogens to understand the connection between infections and cytokine storm syndromes.
METHODS: We recruited children who sought care at the emergency department with fever for ≥3 days. We performed immune profiling using Olink proximity extension assay and flow cytometry. We compared the findings with cases of HLH, MAS, Kawasaki disease (KD), and multisystem inflammatory syndrome in children (MIS-C).
RESULTS: We enrolled 352 febrile patients and studied 110 cases of confirmed common viral infections. We found that Epstein-Barr virus (EBV) uniquely triggered high levels of multiple cytokines (IL-18, IL-27, TNF, FLT3 ligand, and lymphotoxin alpha) and IFN-γ-induced chemokines (CXCL9/10/11 and CCL19). These patterns are similar to the hyperinflammatory response associated with HLH/MAS but are less consistent with the findings in KD and MIS-C. Flow cytometry analysis revealed that CD38+HLA-DR+ T lymphocytes, which are pathogenic cells responsible for IFN-γ production in HLH/MAS, are vastly expanded in patients with acute EBV infection. Cell sorting identified CD38+HLA-DR+ T cells as atypical lymphocytes that are classically associated with acute EBV infection.
CONCLUSION: This work broadens our understanding of common viral infections in children and provides an immunologic basis for the link between EBV infection and HLH/MAS.