ArticleThe Journal of infectious diseases2016
Whole-Exome Sequencing Reveals Mutations in Genes Linked to Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome in Fatal Cases of H1N1 Influenza.
Article in The Journal of infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04336215 (Cohort Study of SARS-CoV-2 Incidence, Transmission, and Disease Severity in Healthcare Workers), which is not on this map. Cited by 94 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Cohort Study of SARS-CoV-2 Incidence, Transmission, and Disease Severity in Healthcare Workers
Who cites it
94 citing papers in PubMed, 1 synthesis or guideline pooled it, 169 citations in OpenAlex.
- Influenza as a Less Commonly Recognized Cause of Hemophagocytic Lymphohistiocytosis: A Systematic Review of Case Reports and Case Series.European journal of haematology · 2026Pooled it
- Mycobacterial Immune Reconstitution Inflammatory Syndrome in HIV is Associated With Protein-Altering Variants in Hemophagocytic Lymphohistiocytosis-Related Genes.The Journal of infectious diseases · 2023Trial
- Adults with septic shock and extreme hyperferritinemia exhibit pathogenic immune variation.Genes and immunity · 2019Trial
- Complexities in the Diagnostic Evaluation and Treatment of Infant Hemophagocytic Lymphohistiocytosis.Hematology reports · 2026Article
- MICBG406A polymorphism reduces risk of mechanical ventilation and death during viral acute lung injury.JCI insight · 2025Article
- Hemophagocytic Lymphohistiocytosis Gene Variants in Severe COVID-19 Cytokine Storm Syndrome.Viruses · 2025Article
- Article
- T-ing up the storm: pathogenic cycling lymphocytes in the biology of macrophage activation syndrome.Pediatric rheumatology online journal · 2025Review
- Role of DOCK8 in cytokine storm syndromes.The Journal of allergy and clinical immunology · 2025Article
- Enrichment of Rare Variants of Hemophagocytic Lymphohistiocytosis Genes in Systemic Juvenile Idiopathic Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- Macrophage Activation Syndrome in Viral Sepsis.Viruses · 2024Review
- Review
- Tuberculosis-Associated Hemophagocytic Lymphohistiocytosis: Diagnostic Challenges and Determinants of Outcome.Open forum infectious diseases · 2024Article
- Autoinflammatory Contributors to Cytokine Storm.Advances in experimental medicine and biology · 2024Review
- COVID-19 Pneumonia and Cytokine Storm Syndrome.Advances in experimental medicine and biology · 2024Review
- Cytokine Storm Syndrome Associated with Hemorrhagic Fever and Other Viruses.Advances in experimental medicine and biology · 2024Review
- Genetics of Acquired Cytokine Storm Syndromes : Secondary HLH Genetics.Advances in experimental medicine and biology · 2024Review
- Criteria for Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Laboratory Features and Pathology of Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Genetic insights into MIS-C Post-COVID-19 in Kuwaiti children: investigating monogenic factors.Frontiers in cellular and infection microbiology · 2024Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundSevere H1N1 influenza can be lethal in otherwise healthy individuals and can have features of reactive hemophagocytic lymphohistiocytosis (HLH). HLH is associated with mutations in lymphocyte cytolytic pathway genes, which have not been previously explored in H1N1 influenza.
methodsSixteen cases of fatal influenza A(H1N1) infection, 81% with histopathologic hemophagocytosis, were identified and analyzed for clinical and laboratory features of HLH, using modified HLH-2004 and macrophage activation syndrome (MAS) criteria. Fourteen specimens were subject to whole-exome sequencing. Sequence alignment and variant filtering detected HLH gene mutations and potential disease-causing variants. Cytolytic function of the PRF1 p.A91V mutation was tested in lentiviral-transduced NK-92 natural killer (NK) cells.
resultsDespite several lacking variables, cases of influenza A(H1N1) infection met 44% and 81% of modified HLH-2004 and MAS criteria, respectively. Five subjects (36%) carried one of 3 heterozygous LYST mutations, 2 of whom also possessed the p.A91V PRF1 mutation, which was shown to decrease NK cell cytolytic function. Several patients also carried rare variants in other genes previously observed in MAS.
conclusionsThis cohort of fatal influenza A(H1N1) infections confirms the presence of hemophagocytosis and HLH pathology. Moreover, the high percentage of HLH gene mutations suggests they are risk factors for mortality among individuals with influenza A(H1N1) infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.