ArticleBlood2020
Functional and genetic testing in adults with HLH reveals an inflammatory profile rather than a cytotoxicity defect.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.
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Who cites it
55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).Annals of the rheumatic diseases · 2023Pooled it
- The 2022 EULAR/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS).Arthritis & rheumatology (Hoboken, N.J.) · 2023Pooled it
- CD56-Positive Acute Myeloid Leukemia Complicated by Hemophagocytic Lymphohistiocytosis: A case report and narrative review.Pakistan journal of medical sciences · 2026Article
- Article
- Chimeric antigen receptor T-cell therapies related to immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome: Diagnosis, high-risk factors, and management.Chinese medical journal · 2026Review
- Still's Disease and Autoinflammation: Positioning an Inflammatory Syndrome on the Autoinflammation-Autoimmunity Spectrum.Current rheumatology reports · 2026Review
- Immune dysregulation and exhaustion in EBV- associated hemophagocytic lymphohistiocytosis: insights from single-cell transcriptomics and TCR repertoire analysis.Frontiers in immunology · 2026Article
- Peritoneal effusion as a marker of disease severity in secondary hemophagocytic lymphohistiocytosis: Clinical and immunological insights.SAGE open medicine · 2026Article
- Hemophagocytic lymphohistiocytosis: do we have a solution for TMI (too much inflammation)?Hematology. American Society of Hematology. Education Program · 2025Review
- Perforin Expression and Natural Killer-Cell Proportion as Biomarkers in Secondary Hemophagocytic Lymphohistiocytosis.Medical science monitor : international medical journal of experimental and clinical research · 2025Observational
- Analysis of genes involved in immune response in children with HLH - case series.Pediatric rheumatology online journal · 2025Article
- Histiocyte Society blueprint for hemophagocytic lymphohistiocytosis research: deciphering underlying disease mechanisms to optimize diagnosis and therapy.Haematologica · 2025Review
- Lymphoid and Myeloid Proliferations After Chimeric Antigen Receptor (CAR) T-Cell Therapy: The Pathologist's Perspective.International journal of molecular sciences · 2025Review
- SARS-CoV-2 Pneumonia: Advances in Diagnosis and Treatment.Microorganisms · 2025Review
- Oncogenic Potential of Epstein-Barr Virus in NK and NKT Cells Contribute to the Rapid Deterioration of Hemophagocytic Lymphohistiocytosis.Journal of medical virology · 2025Article
- Immune Effector Cell-associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS).Hematology/oncology clinics of North America · 2025Review
- Perspectives on the current diagnostic and treatment paradigms in secondary hemophagocytic lymphohistiocytosis (HLH).Orphanet journal of rare diseases · 2025Review
- C3 as a predictive and prognostic biomarker in adult hemophagocytic lymphohistiocytosis: a large cohort study in China.Blood advances · 2025Article
- Childhood Langerhans cell histiocytosis hematological involvement: severity associated with BRAFV600E loads.Blood · 2025Article
- An Unusual Case of Extracavitary/Solid Variant Primary Effusion Lymphoma With Associated Hemophagocytic Lymphohistiocytosis.Journal of medical cases · 2025Article
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Authors and funding
14 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory condition. Primary HLH occurs early in life as a result of monogenic biallelic mutations affecting lymphocyte cytotoxicity. Secondary HLH occurs mostly in adults secondary to infection, lymphoma, or rheumatic disease. In this latter setting, lymphocyte cytotoxicity status is not known. We conducted a systematic evaluation of natural killer (NK) cell cytotoxicity in adult patients with secondary HLH. Adult patients with secondary HLH were prospectively studied ex vivo for total lymphocyte count and subtype, NK cell phenotype, perforin expression and degranulation, and natural or antibody-dependent cell cytotoxicity, in comparison with patients affected by the same underlying disease without HLH (disease controls [DCs]) and with healthy controls (HCs). Screening for variants of cytotoxity genes was systematically performed. 68 patients were included in the HLH group and 34 each in the DC and HC groups. In HLH patients, severe and transient lymphopenia, activated NK cell phenotype (eg, increased CD69, ICAM-1, HLADR, and CCR5 expression), and decreased capacity of interferon γ production were observed; mean perforin expression was normal; and degranulation tests and NK cell cytotoxicity were not different from those in DCs. A monoallelic variant of uncertain significance affecting a lymphocyte cytotoxicity gene or the perforin variant A91V was observed in almost 50% of the patients. We detected no major intrinsic cytotoxicity dysfunction in secondary HLH patients compared with DCs and no predicted pathogenic gene variant. The activated NK phenotype profile associated with decreased interferon γ production seems similar to those of other hyperinflammatory diseases such as sepsis or systemic juvenile idiopathic arthritis.
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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.