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Cytokine Storm Related to CD4+ T Cells in Influenza Virus-Associated Acute Necrotizing Encephalopathy

  • Shushu Wang (Department of Pediatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China) ;
  • Dongyao Wang (Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China) ;
  • Xuesong Wang (Department of Pediatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China) ;
  • Mingwu Chen (Department of Pediatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China) ;
  • Yanshi Wang (Reproductive and Genetic Hospital, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China) ;
  • Haoquan Zhou (Department of Pediatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China) ;
  • Yonggang Zhou (Key Laboratory of Immune Response and Immunotherapy, Division of Life Sciences and Medicine, University of Science and Technology of China) ;
  • Yong Lv (Department of Pediatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China) ;
  • Haiming Wei (Key Laboratory of Immune Response and Immunotherapy, Division of Life Sciences and Medicine, University of Science and Technology of China)
  • Received : 2023.09.19
  • Accepted : 2024.04.18
  • Published : 2024.04.30
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Abstract

Acute necrotizing encephalopathy (ANE) is a rare but deadly complication with an unclear pathogenesis. We aimed to elucidate the immune characteristics of H1N1 influenza virus-associated ANE (IANE) and provide a potential therapeutic approach for IANE. Seven pediatric cases from a concentrated outbreak of H1N1 influenza were included in this study. The patients' CD4+ T cells from peripheral blood decreased sharply in number but highly expressed Eomesodermin (Eomes), CD69 and PD-1, companied with extremely high levels of IL-6, IL-8 in the cerebrospinal fluid and plasma. Patient 2, who showed high fever and seizures and was admitted to the hospital very early in the disease course, received intravenous tocilizumab and subsequently showed a reduction in temperature and a stable conscious state 24 h later. In conclusion, a proinflammatory cytokine storm associated with activated CD4+ T cells may cause severe brain pathology in IANE. Tocilizumab may be helpful in treating IANE.

Keywords

Acknowledgement

This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences, Grant No. XDB0490000. This work was also supported by the National Natural Science Foundation of China (Nos. U19A2024, 81930037 to H.W.), the Anhui Natural Science Foundation (No. 2208085J38 to Y.Z.) and the Fundamental Research Funds for the Central Universities (No. YD9110002019 to D.W.). This research has been approved by human research review boards in the in the first affiliated hospital of USTC.

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