ArticleBlood2013
Distinct severity of HLH in both human and murine mutants with complete loss of cytotoxic effector PRF1, RAB27A, and STX11.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02735824 (Genetic Study of Immunodeficiency), which is not on this map. Cited by 40 papers.
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.
Genetic Study of Immunodeficiency: Search for New Genetic Causes for Primary Immunodeficiencies
Who cites it
40 citing papers in PubMed, 75 citations in OpenAlex.
- Trial
- Genetic and molecular approaches for patients with familial hemophagocytic lymphohistiocytosis: a multi-center experience from Mexico.Frontiers in immunology · 2026Article
- Beyond genotype: challenges in predicting disease risk for carriers of biallelic perforin variants.Blood · 2025Article
- Genetic Evaluation of the Patients with Clinically Diagnosed Inborn Errors of Immunity by Whole Exome Sequencing: Results from a Specialized Research Center for Immunodeficiency in Türkiye.Journal of clinical immunology · 2024Article
- The NLRP3 inflammasome is essential for IL-18 production in a murine model of macrophage activation syndrome.Disease models & mechanisms · 2024Article
- Patients and mice with deficiency in the SNARE protein SYNTAXIN-11 have a secondary B cell defect.The Journal of experimental medicine · 2024Article
- A novel machine learning-derived four-gene signature predicts STEMI and post-STEMI heart failure.Biomolecules & biomedicine · 2024Article
- The NLRP3 inflammasome is essential for IL-18 production in a murine model of macrophage activation syndrome.bioRxiv : the preprint server for biology · 2024Article
- Heterogeneity of macrophage activation syndrome and treatment progression.Frontiers in immunology · 2024Review
- Murine Models of Familial Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- CD8Advances in experimental medicine and biology · 2024Review
- Immunology of Cytokine Storm Syndromes: Natural Killer Cells.Advances in experimental medicine and biology · 2024Review
- The Multifaceted Immunology of Cytokine Storm Syndrome.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Article
- The hyperinflammatory spectrum: from defects in cytotoxicity to cytokine control.Frontiers in immunology · 2023Review
- Insights into the cellular pathophysiology of familial hemophagocytic lymphohistiocytosis.Frontiers in immunology · 2023Review
- Novel RAB27A Variant Associated with Late-Onset Hemophagocytic Lymphohistiocytosis Alters Effector Protein Binding.Journal of clinical immunology · 2022Article
- Histiocytic disorders.Nature reviews. Disease primers · 2021Review
- Attenuating the Effects of Novel COVID-19 (SARS-CoV-2) Infection-Induced Cytokine Storm and the Implications.Journal of inflammation research · 2021Review
- Digenic Inheritance: Evidence and Gaps in Hemophagocytic Lymphohistiocytosis.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inherited defects of granule-dependent cytotoxicity led to the life-threatening immune disorder hemophagocytic lymphohistiocytosis (HLH), characterized by uncontrolled CD8 T-cell and macrophage activation. In a cohort of HLH patients with genetic abnormalities expected to result in the complete absence of perforin, Rab27a, or syntaxin-11, we found that disease severity as determined by age at HLH onset differed significantly, with a severity gradient from perforin (early onset) > Rab27a > syntaxin-11 (late onset). In parallel, we have generated a syntaxin-11-deficient (Stx11(-/-)) murine model that faithfully reproduced the manifestations of HLH after lymphocytic choriomeningitis virus (LCMV) infection. Stx11(-/-) murine lymphocytes exhibited a degranulation defect that could be rescued by expression of human syntaxin-11 but not expression of a C-terminal-truncated mutant. Comparison of the characteristics of LCMV infection-induced HLH in the murine counterparts of the 3 human conditions revealed a similar gradient in the phenotypic severity of HLH manifestations. Strikingly, the severity of HLH was not correlated with the LCMV load and not fully with differences in the intensity of cytotoxic activity. The capacity of antigen presentation differed in vivo between Rab27a- and Syntaxin-11-deficient mutants. Our data indicate that cytotoxic effectors may have other immune-regulatory roles in addition to their role in controlling viral replication.
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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.