ArticlePloS one2019
The interferon-gamma pathway is selectively up-regulated in the liver of patients with secondary hemophagocytic lymphohistiocytosis.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- [Clinical characterization and prognosis of connective tissue disease-associated hemophago-cytic syndrome in adults].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2026Article
- Beyond the Storm: CXCL9 and the New Era of Precision Hemophagocytic Lymphohistiocytosis Diagnostics.Diagnostics (Basel, Switzerland) · 2026Review
- Hepatic Manifestations in Systemic Juvenile Idiopathic Arthritis and Macrophage Activation Syndrome.The Journal of rheumatology · 2026Article
- CXCL9 as a novel prognostic marker to identify high-risk adults with hemophagocytic lymphohistiocytosis.Blood · 2026Article
- STAT1 drives the immune landscape of murine Toll-like receptor 9-induced liver inflammation.JHEP reports : innovation in hepatology · 2026Article
- Peritoneal effusion as a marker of disease severity in secondary hemophagocytic lymphohistiocytosis: Clinical and immunological insights.SAGE open medicine · 2026Article
- Therapeutic antibodies in oncology: an immunopharmacological overview.Cancer immunology, immunotherapy : CII · 2024Review
- Liver Dysfunction in Adult Hemophagocytic Lymphohistiocytosis: A Narrative Review.Advances in therapy · 2024Review
- The 4th NextGen therapies for SJIA and MAS: part 2 phenotypes of refractory SJIA and the landscape for clinical trials in refractory SJIA.Pediatric rheumatology online journal · 2024Article
- Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients.Frontiers in immunology · 2024Article
- Type 1 Interferon-Stimulated Gene Expression and Disease Activity in Pediatric Rheumatic Diseases: No Composite Scores Needed?ACR open rheumatology · 2023Article
- 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
- Familial hemophagocytic lymphohistiocytosis hepatitis is mediated by IFN-γ in a predominantly hepatic-intrinsic manner.PloS one · 2022Article
- Characterization of HLH-like manifestations as a CRS variant in patients receiving CD22 CAR T cells.Blood · 2021Article
- 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
- The cytokine storms of COVID-19, H1N1 influenza, CRS and MAS compared. Can one sized treatment fit all?Cytokine · 2021Review
- International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Non-proliferative and Proliferative Lesions of the Non-human Primate (Journal of toxicologic pathology · 2021Review
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aim of this study was to investigate the activation of the IFNγ pathway in the affected liver and in the blood of patients with secondary hemophagocytic lymphohistiocytosis (sHLH). To this purpose, the mRNA expression levels of IFNG and IFNγ-inducible genes as well as Tyrosine (701)-phosphorylated signal transducer and activator of transcription 1 (STAT1) protein levels were evaluated in the liver and in peripheral blood mononuclear cells (PBMCs) of three patients with sHLH with predominant liver involvement. The mRNA expression levels of IFNG and IFNγ-inducible genes were markedly higher in patient livers compared to control livers and to one disease control liver. Conversely, slight differences in the expression levels of Type I IFN-inducible genes and other classical inflammatory cytokine genes were found. Further supporting the activation of the IFNγ pathway, higher protein levels of phosphorylated and total STAT1 were detected in patient livers compared to control livers. When the expression of the same genes analysed in liver tissues was evaluated in PBMCs collected from 2 out of 3 patients before the liver biopsy, we found that mRNA levels of IFNγ-inducible genes were markedly increased. Accordingly, high circulating levels of IFNγ-inducible CXCL9 were observed in patients. Altogether, these data demonstrate the selective and marked up-regulation of the IFNγ pathway in the liver tissue and blood of patients with active sHLH. Finally, we show that measurement of circulating CXCL9 levels and evaluation of IFNγ-inducible gene expression levels in PBMCs may represent a new valid tool to better identify patients with suspected HLH with predominant liver involvement.
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