ArticleThe Journal of allergy and clinical immunology2016
Genetic predisposition to hemophagocytic lymphohistiocytosis: Report on 500 patients from the Italian registry.
Article in The Journal of allergy and clinical immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 2 of them syntheses that pooled it.
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Who cites it
92 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Evaluating whole genome sequencing for rare diseases in newborn screening: evidence synthesis from a series of systematic reviews.Health technology assessment (Winchester, England) · 2025Pooled it
- Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis.Journal of clinical immunology · 2020Pooled it
- HLHRUXO: a prospective trial of a ruxolitinib-containing regimen for children with hemophagocytic lymphohistiocytosis.Blood advances · 2026Trial
- Adults with septic shock and extreme hyperferritinemia exhibit pathogenic immune variation.Genes and immunity · 2019Trial
- Trial
- Clinical-Pathological Conference Series from the Medical University of Graz : Case No 186: A 33-year-old plumber with fever and acute liver injury.Wiener klinische Wochenschrift · 2026Article
- The DRESS/HLH Overlap Syndrome: A Systematic Review of Clinical Features, Triggers, and Outcomes.Journal of clinical medicine · 2026Review
- Spectrum of Primary Hemophagocytic Lymphohistiocytosis-Associated Gene Mutations in Chinese Patients.MedComm · 2026Article
- Reactive and therapy induced bone marrow changes linked to systemic infectious and non-infectious disorders including MAS/HLH report from the European association for haematopathology, Dubrovnik 2024.Virchows Archiv : an international journal of pathology · 2026Article
- Digenic and multigenic heterozygous FHL genotypes are common but clinically silent in the general population.Blood advances · 2026Article
- CXCL9 as a novel prognostic marker to identify high-risk adults with hemophagocytic lymphohistiocytosis.Blood · 2026Article
- Consensus recommendations for the diagnosis and management of hemophagocytic lymphohistiocytosis in the Gulf Cooperation Council: a modified Delphi approach.Frontiers in immunology · 2026Article
- Case Report: Hyperinflammatory toxicities after Epstein-Barr virus-associated post-transplant lymphoproliferative disorder and hemophagocytic lymphohistiocytosis in a pediatric kidney transplant recipient.Frontiers in immunology · 2026Article
- Lymphoproliferation in Inborn Errors of Immunity: Mechanisms, Manifestations and Clinical Management, with a Focus on ALPID.ImmunoTargets and therapy · 2026Review
- Adult Onset of Type 2 Familial Hemophagocytic Lymphohistiocytosis After SARS-CoV-2 Vaccination with an Unusual Neurological Onset: The Great Mimic.Diagnostics (Basel, Switzerland) · 2025Article
- Analysis of genes involved in immune response in children with HLH - case series.Pediatric rheumatology online journal · 2025Article
- Article
- Inborn errors of immunity-associated gene variants in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.International journal of hematology · 2025Article
- Article
- Haemophagocytic lymphohistiocytosis in critically ill adults: a single-centre retrospective ICU cohort study.Frontiers in medicine · 2025Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors.
Funding
Abstract
backgroundHemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease affecting mostly children but also adults and characterized by hyperinflammatory features. A subset of patients, referred to as having familial hemophagocytic lymphohistiocytosis (FHL), have various underlying genetic abnormalities, the frequencies of which have not been systematically determined previously.
objectiveThis work aims to further our understanding of the pathogenic bases of this rare condition based on an analysis of our 25 years of experience.
methodsFrom our registry, we have analyzed a total of 500 unselected patients with HLH.
resultsBiallelic pathogenic mutations defining FHL were found in 171 (34%) patients; the proportion of FHL was much higher (64%) in patients given a diagnosis during the first year of life. Taken together, mutations of the genes PRF1 (FHL2) and UNC13D (FHL3) accounted for 70% of cases of FHL. Overall, a genetic diagnosis was possible in more than 90% of our patients with FHL. Perforin expression and the extent of degranulation have been more useful for diagnosing FHL than hemophagocytosis and the cytotoxicity assay. Of 281 (56%) patients classified as having "sporadic" HLH, 43 had monoallelic mutations in one of the FHL-defining genes. Given this gene dosage effect, FHL is not strictly recessive.
conclusionWe suggest that the clinical syndrome HLH generally results from the combined effects of an exogenous trigger and genetic predisposition. Within this combination, different weights of exogenous and genetic factors account for the wide disease spectrum that ranges from HLH secondary to severe infection to FHL.
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