ReviewGenes and immunity2020
The genetics of macrophage activation syndrome.
Review in Genes and immunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 3 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 3 syntheses or guidelines pooled it, 90 citations in OpenAlex.
- Is a variant of uncertain significance always 'insignificant'? A systematic review on PRF1 A91V in Hemophagocytic Lymphohistocytosis and comparative analysis with Still's disease.Orphanet journal of rare diseases · 2026Pooled it
- Retinal manifestations in patients with SARS-CoV-2 infection and pathogenetic implications: a systematic review.International ophthalmology · 2022Pooled it
- Severe COVID-19: what have we learned with the immunopathogenesis?Advances in rheumatology (London, England) · 2020Pooled it
- Prognostic impact of germline and somatic variants in lymphoma-associated haemophagocytic lymphohistiocytosis.British journal of haematology · 2026Article
- Pathogenic and genetic landscape of Still's disease across ages, with new insights into age-related IL-18 patterns.Arthritis research & therapy · 2026Review
- Endosome traffic in rheumatic diseases: mechanistic insights and therapeutic opportunities.Nature reviews. Rheumatology · 2026Review
- Still's Disease and Autoinflammation: Positioning an Inflammatory Syndrome on the Autoinflammation-Autoimmunity Spectrum.Current rheumatology reports · 2026Review
- Cytokine storm.Nature reviews. Disease primers · 2026Review
- Beyond genotype: challenges in predicting disease risk for carriers of biallelic perforin variants.Blood · 2025Article
- Role of DOCK8 in cytokine storm syndromes.The Journal of allergy and clinical immunology · 2025Article
- Weal and woe of interleukin-18 in the T cell therapy of cancer.Journal for immunotherapy of cancer · 2025Review
- Synergistic hyperinflammation in IgA vasculitis complicated by varicella-induced HLH: a case report.Frontiers in immunology · 2025Article
- Genetics of progressive multifocal leukoencephalopathy: update on case reports with an inborn error of immunity and risk variants found in drug-linked cases.Frontiers in neurology · 2025Review
- Enrichment of Rare Variants of Hemophagocytic Lymphohistiocytosis Genes in Systemic Juvenile Idiopathic Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- New discoveries in the genetics and genomics of systemic juvenile idiopathic arthritis.Expert review of clinical immunology · 2024Review
- Ocular Implications of COVID-19 Infection and Vaccine-Related Adverse Events.Journal of personalized medicine · 2024Review
- The NLRP3 inflammasome is essential for IL-18 production in a murine model of macrophage activation syndrome.Disease models & mechanisms · 2024Article
- TAFRO Syndrome and COVID-19.Biomedicines · 2024Review
- The NLRP3 inflammasome is essential for IL-18 production in a murine model of macrophage activation syndrome.bioRxiv : the preprint server for biology · 2024Article
- Prognostic factors in patients with secondary hemophagocytic lymphohistioc ytosis in a Chinese cohort.Annals of hematology · 2024Observational
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Macrophage activation syndrome (MAS), or secondary hemophagocytic lymphohistiocytosis (HLH), is a cytokine storm syndrome associated with multi-organ system dysfunction and high mortality rates. Laboratory and clinical features resemble primary HLH, which arises in infancy (1 in 50,000 live births) from homozygous mutations in various genes critical to the perforin-mediated cytolytic pathway employed by NK cells and cytotoxic CD8 T lymphocytes. MAS/secondary HLH is about ten times more common and typically presents beyond infancy extending into adulthood. The genetics of MAS are far less defined than for familial HLH. However, the distinction between familial HLH and MAS/secondary HLH is blurred by the finding of heterozygous perforin-pathway mutations in MAS patients, which may function as hypomorphic or partial dominant-negative alleles and contribute to disease pathogenesis. In addition, mutations in a variety of other pathogenic pathways have been noted in patients with MAS/secondary HLH. Many of these genetically disrupted pathways result in a similar cytokine storm syndrome, and can be broadly categorized as impaired viral control (e.g., SH2P1A), dysregulated inflammasome activity (e.g., NLRC4), other immune defects (e.g., IKBKG), and dysregulated metabolism (e.g., LIPA). Collectively these genetic lesions likely combine with states of chronic inflammation, as seen in various rheumatic diseases (e.g., still disease), with or without identified infections, to result in MAS pathology as explained by the threshold model of disease. This emerging paradigm may ultimately support genetic risk stratification for high-risk chronic and even acute inflammatory disorders. Moving forward, continued whole-exome and -genome sequencing will likely identify novel MAS gene associations, as well as noncoding mutations altering levels of gene expression.
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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.