SEVERE febrile illnesses in children, which can lead to life-threatening organ dysfunction, are caused by various pathogens and severe inflammatory syndromes. By comparing different illnesses, researchers can identify both shared and unique immune dysfunction patterns that could guide immunomodulation therapy.
The study focused on understanding immune responses in 74 children with multi-system inflammatory syndrome (MIS-C) linked to SARS-CoV-2, alongside children with bacterial or viral infections, Kawasaki disease, and healthy controls. Using techniques such as mass cytometry and cell stimulation, the research revealed critical immune pathways. In MIS-C, neutrophil activation and apoptosis were highly pronounced, a feature also observed in bacterial infections. Both MIS-C and bacterial infections showed signs of memory T cell exhaustion, but viral infections had a distinct immune signature with reduced interferon signalling, highlighting differences in the immune response.
The findings suggest that T cell exhaustion and neutrophil activation are central to MIS-C and bacterial infections, which could explain similar clinical presentations, such as fever and multi-organ involvement. On the other hand, viral infections had lower interferon receptor gene expression, which is an important marker of immune system dysfunction. Additionally, the study explored the potential of using immunomodulators, which have been effective in treating MIS-C and severe cases of COVID-19. The data suggest that understanding immune dysregulation in severe febrile illnesses could lead to more targeted therapies.
The comparison between MIS-C and other severe febrile illnesses in children highlights both shared and distinct immune pathways. Neutrophil activation, T cell exhaustion, and interferon signalling play pivotal roles in the immune response, offering insights into potential therapeutic strategies for these conditions.
Katie Wright, EMJ
Reference
Patel H et al. Shared neutrophil and T cell dysfunction is accompanied by a distinct interferon signature during severe febrile illnesses in children. Nat Commun. 2024;15(1):8224.
