ArticleTranslational research : the journal of laboratory and clinical medicine2017
Use of a mouse model to identify a blood biomarker for IFNγ activity in pediatric secondary hemophagocytic lymphohistiocytosis.
Article in Translational research : the journal of laboratory and clinical medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO).Pediatric blood & cancer · 2019Guideline
- Emapalumab in primary haemophagocytic lymphohistiocytosis and the pathogenic role of interferon gamma: A pharmacometric model-based approach.British journal of clinical pharmacology · 2022Trial
- Emapalumab for severe cytokine release syndrome in solid tumor CAR-T: a case report.Frontiers in oncology · 2025Article
- Low-dose emapalumab treatment in refractory macrophage activation syndrome secondary to adult onset still's disease/systemic lupus erythematosus: insights from nine cases.Frontiers in immunology · 2025Article
- Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms.Journal of hematology & oncology · 2024Review
- Real-world treatment patterns and outcomes in patients with primary hemophagocytic lymphohistiocytosis treated with emapalumab.Blood advances · 2024Article
- Case report: emapalumab treatment for a pediatric Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) patient with cytokine storm enabling allogeneic hematopoietic cell transplantation.Translational pediatrics · 2024Article
- Interferon-γ and its response are determinants of antibody-mediated rejection and clinical outcomes in patients after renal transplantation.Genes and immunity · 2024Article
- Anti-Interferon-γ Therapy for Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Murine Models of Secondary Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Cytokines in Cytokine Storm Syndrome.Advances in experimental medicine and biology · 2024Review
- The History of Macrophage Activation Syndrome in Autoimmune Diseases.Advances in experimental medicine and biology · 2024Review
- Secondary hemophagocytic lymphohistiocytosis in children (Review).Experimental and therapeutic medicine · 2023Review
- The Liver in Hemophagocytic Lymphohistiocytosis: Not an Innocent Bystander.Journal of pediatric gastroenterology and nutrition · 2023Review
- CXCL9 inhibition does not ameliorate disease in murine models of both primary and secondary hemophagocytic lymphohistiocytosis.Scientific reports · 2023Article
- Cytokine nanosponges suppressing overactive macrophages and dampening systematic cytokine storm for the treatment of hemophagocytic lymphohistiocytosis.Bioactive materials · 2023Article
- Familial hemophagocytic lymphohistiocytosis hepatitis is mediated by IFN-γ in a predominantly hepatic-intrinsic manner.PloS one · 2022Article
- Targeting interferon-γ in hyperinflammation: opportunities and challenges.Nature reviews. Rheumatology · 2021Review
- IFN-γ signature in the plasma proteome distinguishes pediatric hemophagocytic lymphohistiocytosis from sepsis and SIRS.Blood advances · 2021Article
- Immunological analysis of the murine anti-CD3-induced cytokine release syndrome model and therapeutic efficacy of anti-cytokine antibodies.European journal of immunology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Life-threatening cytokine release syndromes include primary (p) and secondary (s) forms of hemophagocytic lymphohistiocytosis (HLH). Below detection in healthy individuals, interferon γ (IFNγ) levels are elevated to measurable concentrations in these afflictions suggesting a central role for this cytokine in the development and maintenance of HLH. Mimicking an infection-driven model of sHLH in mice, we observed that the tissue-derived levels of IFNγ are actually 500- to 2000-fold higher than those measured in the blood. To identify a blood biomarker, we postulated that the IFNγ gene products, CXCL9 and CXCL10 would correlate with disease parameters in the mouse model. To translate this into a disease relevant biomarker, we investigated whether CXCL9 and CXCL10 levels correlated with disease activity in pediatric sHLH patients. Our data demonstrate that disease control in mice correlates with neutralization of IFNγ activity in tissues and that the 2 chemokines serve as serum biomarkers to reflect disease status. Importantly, CXCL9 and CXCL10 levels in pediatric sHLH were shown to correlate with key disease parameters and severity in these patients. Thus, the translatability of the IFNγ-biomarker correlates from mouse to human, advocating the use of serum CXCL9 or CXCL10 as a means to monitor total IFNγ activity in patients with sHLH.
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