The role of miRNAs as potential early warning biomarkers for influenza-associated acute necrotizing encephalopathy in children
Nikhil Prasad Fact checked by:Thailand Medical News Team Mar 22, 2025 1 day, 11 hours, 43 minutes ago
Medical News: A team of scientists from China has uncovered important new clues into why some children develop a rare but life-threatening brain condition called acute necrotizing encephalopathy or ANE following an influenza infection. By analyzing blood samples of pediatric patients, the researchers discovered two specific microRNAs (miRNAs) that were significantly lower in children who developed severe neurological complications.
The role of miRNAs as potential early warning biomarkers for influenza-associated acute
necrotizing encephalopathy in children
The groundbreaking study was led by researchers from Beijing Children’s Hospital at Capital Medical University and Shenzhen Children’s Hospital. It provides new insights into how miRNAs, tiny molecules that help regulate genes, might serve as early warning signs for this dangerous condition. This
Medical News report outlines the details of their findings and how they could pave the way for better diagnosis and treatment.
Understanding ANE and Its Dangers
Acute necrotizing encephalopathy is a devastating and fast-progressing disease that affects the brain. It typically arises as a secondary complication following viral infections like influenza or even COVID-19. Children, particularly those under the age of five and of Asian descent, appear to be especially at risk. ANE can lead to severe brain damage, coma, or even death within a short time - sometimes just 24 hours after symptoms begin.
At present, there is no specific treatment for ANE. Doctors often resort to immunosuppressive therapies like steroids and intravenous immunoglobulin (IVIG), along with antivirals and supportive care. Yet, even with these interventions, outcomes are often grim. Identifying biomarkers that could alert doctors early on to the onset of ANE is critical to improving survival rates.
The Study Design and Approach
To investigate, researchers enrolled six pediatric patients who had tested positive for influenza. Three had developed ANE (the severe group), while the other three had a milder form of the illness with no neurological symptoms. Blood samples were collected from all six children and analyzed using next-generation sequencing technology to detect changes in miRNA expression.
miRNAs are small, non-coding RNAs that can regulate gene activity and play critical roles in how the body responds to infection and inflammation. Changes in their levels can indicate the presence of disease and even predict outcomes.
Key Findings
The researchers identified 91 miRNAs that showed significant differences between the two groups. Of these, 24 miRNAs were found to be upregulated, while 67 were downregulated in the children with ANE. Further testing confirmed that two specific miRNAs - hsa-miR-4657 and hsa-miR-342-3p - were drastically reduced in the severe group compared to those with mild illness.
These two miRNAs have been previously linked to inflammation and immune system regulation. In particular, hs
a-miR-342-3p is known to suppress inflammatory proteins like IL-6 and TNF-α, both of which are often elevated during cytokine storms - an intense immune response that is thought to drive much of the brain damage seen in ANE. The drop in these protective miRNAs may therefore worsen inflammation and increase the risk of severe complications.
Pathway Analysis Provides Further Insight
Using Gene Ontology (GO) and KEGG pathway analysis, the researchers found that the genes affected by these miRNAs were most strongly associated with processes like cellular regulation, ion binding, and calcium signaling. Importantly, pathways involved in axon guidance - the mechanism by which brain cells connect with each other - were also implicated.
This is especially relevant because damage to axons and disruptions in neural communication are hallmarks of ANE. The enrichment of genes related to calcium signaling and axonal development suggests that miRNA imbalances might directly impact brain function, potentially offering targets for future therapeutic intervention.
Clinical Observations Match Molecular Data
In addition to molecular findings, clinical data from the patients supported the results. Children in the severe group showed higher levels of inflammatory markers like CRP, IL-6, and procalcitonin. One child died within 24 hours of admission, underscoring the rapid and deadly course of the disease. Immune cell imbalances were also more pronounced in this group, with disruptions seen in T-cells, B-cells, and natural killer cells.
These combined factors indicate that miRNA changes are likely part of a larger picture involving immune system overreaction and neuroinflammation.
Conclusion
This important study highlights the role of miRNAs as potential early warning biomarkers for influenza-associated acute necrotizing encephalopathy in children. The identification of hsa-miR-4657 and hsa-miR-342-3p as significantly downregulated in severe cases offers promising avenues for future diagnostic tests or treatments. While further research with larger patient groups is necessary, these findings could eventually help doctors intervene sooner and save lives. Understanding how these tiny RNA fragments influence the body’s response to influenza-related brain damage may be a critical step in preventing the devastating outcomes of ANE.
The study findings were published in the peer reviewed journal Infection, Genetics and Evolution.
https://www.sciencedirect.com/science/article/pii/S1567134825000231
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