ArticleFrontiers in immunology2013
Elevated Granzyme B in Cytotoxic Lymphocytes is a Signature of Immune Activation in Hemophagocytic Lymphohistiocytosis.
Article in Frontiers in immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO).Pediatric blood & cancer · 2019Guideline
- Immune function in X-linked retinoschisis subjects in an AAV8-RS1 phase I/IIa gene therapy trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Trial
- Prognostic Value of Skin Lesion Characteristics in Subcutaneous Panniculitis-Like T-Cell Lymphoma: A Retrospective Cohort Study Assessing the Applicability of T Category of the TNM Classification for Primary Cutaneous Lymphomas Other Than Mycosis Fungoides and Sézary Syndrome.International journal of dermatology · 2026Article
- Optoregulated mRNA Delivery Controls Pleiotropic Immune Signaling for Tumor-Targeted Therapy.Angewandte Chemie (International ed. in English) · 2025Article
- Case Report: Late-onset primary hemophagocytic lymphohistiocytosis leading to the diagnosis of Griscelli syndrome type 2 in a young woman with phenotypically inapparent partial albinism.Frontiers in immunology · 2025Article
- Comprehensive evaluation of immune dysregulation in secondary hemophagocytic lymphohistiocytosis.Virulence · 2024Article
- Crosstalk Between NK Cell Receptors and Tumor Membrane Hsp70-Derived Peptide: A Combined Computational and Experimental Study.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Immune Cytolytic Activity and Strategies for Therapeutic Treatment.International journal of molecular sciences · 2024Review
- Large extracellular vesicles derived from human regulatory macrophages (L-EVJournal of molecular medicine (Berlin, Germany) · 2023Article
- Successful Recovery from Severe Fever with Thrombocytopenia Syndrome and Hemophagocytic Lymphohistiocytosis with Standard Treatment and a Calcium Channel Blocker of Nicardipine Hydrochloride.Internal medicine (Tokyo, Japan) · 2023Article
- Article
- A novel lipidic peptide with potential to promote balanced effector-regulatory T cell responses.Scientific reports · 2022Article
- Cytolytic CD4Frontiers in immunology · 2022Review
- NK- and T-cell granzyme B and K expression correlates with age, CMV infection and influenza vaccine-induced antibody titres in older adults.Frontiers in aging · 2022Article
- Metabolic parameters on baselineFrontiers in medicine · 2022Article
- EGCG Inhibits Tumor Growth in Melanoma by Targeting JAK-STAT Signaling and Its Downstream PD-L1/PD-L2-PD1 Axis in Tumors and Enhancing Cytotoxic T-Cell Responses.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Non-invasive Detection of Immunotherapy-Induced Adverse Events.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Granzyme B in peripheral blood mononuclear cells as a measure of cell-mediated immune response in paraneoplastic neurological syndromes and malignancy.Cancer immunology, immunotherapy : CII · 2021Article
- Four Biomarkers Linked to Activation of Cluster of Differentiation 8-Positive Lymphocytes Predict Clinical Outcomes in Pediatric Acute Liver Failure.Hepatology (Baltimore, Md.) · 2021Observational
- Rapid Identification of the Tumor-Specific Reactive TIL RepertoireFrontiers in immunology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with hemophagocytic lymphohistiocytosis (HLH) exhibit immune hyper-activation as a consequence of genetic defects in secretory granule proteins of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. Murine models of HLH demonstrate significant activation of CTL as central to the disease pathogenesis, but evaluation of CTL and NK activation in children with HLH or inflammatory conditions is not well described. CD8 T cells only express granzyme B (GrB) following stimulation and differentiation into CTL; therefore, we reasoned that GrB expression may serve as a signature of CTL activation. It is unknown whether human NK cells are similarly activated in vivo, as marked by increased granule proteins. Perforin and GrB levels are measured in both CTL and NK cells by flow cytometry to diagnose perforin deficiency. We retrospectively compared GrB expression in blood samples from 130 children with clinically suspected and/or genetically defined HLH to age-matched controls. As predicted, CD8 expressing GrB cells were increased in HLH, regardless of genetic etiology. Remarkably, the GrB protein content also increased in NK cells in patients with HLH and decreased following immunosuppressive therapy. This suggests that in vivo activation of NK cells occurs in hyper-inflammatory conditions. We conclude that increased detection of GrB in CTL and NK are an immune signature for lymphocyte activation in HLH, irrespective of genetic subtype and may also be a useful measure of immune activation in other related conditions.
Indexed as
Identifiers
What OpenQuestion holds
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.