ArticleBlood2021
T-cell activation profiles distinguish hemophagocytic lymphohistiocytosis and early sepsis.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 2 of them syntheses that pooled it.
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Who cites it
88 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Systemic juvenile idiopathic arthritis and adult-onset Still's disease are the same disease: evidence from systematic reviews and meta-analyses informing the 2023 EULAR/PReS recommendations for the diagnosis and management of Still's disease.Annals of the rheumatic diseases · 2024Pooled it
- HLH and Recurrent EBV Lymphoma as the presenting manifestation of MAGT1 Deficiency: A Systematic Review of the Expanding Disease Spectrum.Journal of clinical immunology · 2024Pooled it
- Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome during treatment with the bivalent CD20xCD3 bispecific antibody glofitamab.Haematologica · 2026Article
- HLA-DRRespiratory research · 2026Article
- Pediatric Sepsis: Evolving Subphenotypes, Overlap Syndromes, and the Path to Precision Therapies.Clinics in chest medicine · 2026Review
- High PD-1 expression in pre-treatment peripheral lymphocytes associated with poor immune checkpoint inhibitor response in patients with recurrent or metastatic head and neck squamous cell carcinoma.Cancer immunology, immunotherapy : CII · 2026Article
- Integrative analysis of transcriptome and single-cell sequencing combined with experimental validation identifies biomarkers associated with T cell and senescence in sepsis.Scientific reports · 2026Article
- STAT1 drives the immune landscape of murine Toll-like receptor 9-induced liver inflammation.JHEP reports : innovation in hepatology · 2026Article
- A case report of hemophagocytic lymphohistiocytosis secondary to tislelizumab and bevacizumab combination therapy for renal cell carcinoma.Translational cancer research · 2026Article
- Successful management of scrub typhus-associated hemophagocytic lymphohistiocytosis with doxycycline and immunomodulation: a case report.Frontiers in pediatrics · 2026Article
- Article
- Hyperinflammatory Syndrome of Unknown Origin Complicated by Shock, DIC, Intracranial Hemorrhage and Spontaneous Splenic Rupture: A Case Report.Clinical medicine insights. Case reports · 2026Article
- Identification of distinct immune subtypes in sepsis through dual immunomarker trajectory.Annals of intensive care · 2026Article
- Contrasting outcomes of visceral leishmaniasis in two patients with membranous nephropathy receiving immunosuppressive therapy: a case report.Frontiers in immunology · 2026Article
- HLA-DR+ CD8+ T lymphocytes as an alternative T-cell activation marker in pediatric HLH: A real-life study.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026Article
- Profound hematologic instability in consanguinity-associated familial hemophagocytic lymphohistiocytosis: a pediatric case report.Annals of medicine and surgery (2012) · 2025Article
- Article
- Histiocyte Society blueprint for hemophagocytic lymphohistiocytosis research: deciphering underlying disease mechanisms to optimize diagnosis and therapy.Haematologica · 2025Review
- BCL-2 Inhibitor Regulates Number, Function, and Antitumor Immunity of T Cells by Influencing Glycolysis in AML.Cancer science · 2025Article
- Cytotoxic T-cell activation profile in critically ill children with malignancies and hemophagocytic lymphohistiocytosis.Pediatric research · 2025Article
28 more citing papers are in PubMed but not listed here.
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16 authors.
Funding
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a fatal disorder of immune hyperactivation that has been described as a cytokine storm. Sepsis due to known or suspected infection has also been viewed as a cytokine storm. Although clinical similarities between these syndromes suggest similar immunopathology and may create diagnostic uncertainty, distinguishing them is critical as treatments are widely divergent. We examined T-cell profiles from children with either HLH or sepsis and found that HLH is characterized by acute T-cell activation, in clear contrast to sepsis. Activated T cells in patients with HLH were characterized as CD38high/HLA-DR+ effector cells, with activation of CD8+ T cells being most pronounced. Activated T cells were type 1 polarized, proliferative, and displayed evidence of recent and persistent activation. Circulating activated T cells appeared to be broadly characteristic of HLH, as they were seen in children with and without genetic lesions or identifiable infections and resolved with conventional treatment of HLH. Furthermore, we observed even greater activation and type 1 polarization in tissue-infiltrating T cells, described here for the first time in a series of patients with HLH. Finally, we observed that a threshold of >7% CD38high/HLA-DR+ cells among CD8+ T cells had strong positive and negative predictive value for distinguishing HLH from early sepsis or healthy controls. We conclude that the cytokine storm of HLH is marked by distinctive T-cell activation whereas early sepsis is not, and that these 2 syndromes can be readily distinguished by T-cell phenotypes.
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