Observational studyThe Journal of infectious diseases2022
Hyperinflammatory Syndrome, Natural Killer Cell Function, and Genetic Polymorphisms in the Pathogenesis of Severe Dengue.
Observational study in The Journal of infectious diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- A systematic mapping review of therapeutic clinical trials in dengue.PLoS neglected tropical diseases · 2026Pooled it
- Dengue virus infection.Nature reviews. Disease primers · 2026Review
- Dengue and severe dengue.Clinical microbiology reviews · 2025Review
- Interplay between innate immune cells and inflammatory mediators in dengue infection: an evolving therapeutic paradigm.Expert reviews in molecular medicine · 2025Review
- Early NK-cell and T-cell dysfunction marks progression to severe dengue in patients with obesity and healthy weight.Nature communications · 2025Article
- Dysregulated immune cell responses in severe dengue pathogenesis.Frontiers in immunology · 2025Review
- Immunomodulation in dengue: towards deciphering dengue severity markers.Cell communication and signaling : CCS · 2024Review
- Increased CD56 expression after photodynamic therapy indicates an increased natural killer cell count following early photodynamic therapy for cutaneous squamous cell carcinoma.Oncology letters · 2024Article
- Macrophage Activation Syndrome in Viral Sepsis.Viruses · 2024Review
- Tuberculosis-Associated Hemophagocytic Lymphohistiocytosis: Diagnostic Challenges and Determinants of Outcome.Open forum infectious diseases · 2024Article
- Endothelial and inflammatory pathophysiology in dengue shock: New insights from a prospective cohort study in Vietnam.PLoS neglected tropical diseases · 2024Observational
- Anakinra for dengue patients with hyperinflammation: protocol for a randomized double-blind placebo-controlled trial.Wellcome open research · 2024Article
- Atopic Dermatitis Immune Dysregulation as Dengue Predisposing Factor.Journal of inflammation research · 2024Review
- Kinetics of cardiovascular and inflammatory biomarkers in paediatric dengue shock syndrome.Oxford open immunology · 2024Article
- Immune response to arbovirus infection in obesity.Frontiers in immunology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundSevere dengue, characterized by shock and organ dysfunction, is driven by an excessive host immune response. We investigated the role of hyperinflammation in dengue pathogenesis.
methodsPatients recruited into an observational study were divided into 3 plasma leak severity grades. Hyperinflammatory biomarkers were measured at 4 time points. Frequencies, activation, and cytotoxic potential of natural killer (NK) cells were analyzed by flow cytometry. RNA was extracted from sorted CD56+ NK cells and libraries were prepared using SMART-Seq and sequenced using HiSeq3000 (Illumina).
resultsSixty-nine patients were included (grade 0, 42 patients; grade 1, 19 patients; grade 2, 8 patients). Patients with grade 2 leakage had higher biomarkers than grade 0, including higher peak ferritin levels (83.3% vs 45.2%) and H-scores (median, 148.5 vs 105.5). NK cells from grade 2 patients exhibited decreased expression of perforin and granzyme B and activation markers. RNA sequencing revealed 3 single-nucleotide polymorphisms in NK cell functional genes associated with more severe leakage-NK cell lectin-like receptor K1 gene (KLRK1) and perforin 1 (PRF1).
conclusionsFeatures of hyperinflammation are associated with dengue severity, including higher biomarkers, impaired NK cell function, and polymorphisms in NK cell cytolytic function genes (KLRK1 and PRF1). Trials of immunomodulatory therapy in these patients is now warranted.
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Registered trials
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