ArticleJCI insight2016
A xenograft model of macrophage activation syndrome amenable to anti-CD33 and anti-IL-6R treatment.
Article in JCI insight, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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.
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Who cites it
34 citing papers in PubMed, 53 citations in OpenAlex.
- Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases.The Journal of clinical investigation · 2020Trial
- Pathology associated with human CAR T cell administration in NOD.Cg-Veterinary pathology · 2026Article
- NeoThy™ immune-humanized mice can produce anti-drug antibodies to support immunogenicity assessment for biological drug products.Frontiers in immunology · 2026Article
- Monocyte/macrophages may exert prominent roles in macrophage activation syndrome.Annals of hematology · 2025Article
- Preclinical ex vivo and in vivo models to study immunotherapy agents and their combinations as predictive tools toward the clinic.Journal for immunotherapy of cancer · 2025Review
- The pathophysiology of hemophagocytic lympho-histiocytosis (HLH) syndrome and insights from animal models.Clinical and experimental immunology · 2025Review
- Engrafted NSG-SGM3 humanized mice spontaneously produce human immunoglobulins including IgE.Frontiers in immunology · 2025Article
- Humanization with CD34-positive hematopoietic stem cells in NOG-EXL mice results in improved long-term survival and less severe myeloid cell hyperactivation phenotype relative to NSG-SGM3 mice.Veterinary pathology · 2024Article
- Single-cell RNA sequencing reveals peripheral blood leukocyte responses to spinal cord injury in mice with humanised immune systems.Journal of neuroinflammation · 2024Article
- Identification of miRNAs that target Fcγ receptor-mediated phagocytosis during macrophage activation syndrome.Frontiers in immunology · 2024Article
- Heterogeneity of macrophage activation syndrome and treatment progression.Frontiers in immunology · 2024Review
- IL-6 Blockade in Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Autoinflammatory Contributors to Cytokine Storm.Advances in experimental medicine and biology · 2024Review
- Cytokines in Cytokine Storm Syndrome.Advances in experimental medicine and biology · 2024Review
- Current Advances in Humanized Mouse Models for Studying NK Cells and HIV Infection.Microorganisms · 2023Review
- Mouse models of systemic juvenile idiopathic arthritis and macrophage activation syndrome.Arthritis research & therapy · 2023Review
- Humanized mouse models for immuno-oncology research.Nature reviews. Clinical oncology · 2023Review
- Next-generation humanized NSG-SGM3 mice are highly susceptible toFrontiers in immunology · 2023Article
- Humanized Ovarian Cancer Patient-Derived Xenografts for Improved Preclinical Evaluation of Immunotherapies.Cancers · 2022Article
- Innate Immune Reconstitution in Humanized Bone Marrow-Liver-Thymus (HuBLT) Mice Governs Adaptive Cellular Immune Function and Responses to HIV-1 Infection.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Transgenic expression of key myelosupportive human cytokines in immune-deficient mice corrects for the lack of cross-species activities of stem cell factor (SCF), IL-3, and GM-CSF. When engrafted with human umbilical cord blood (UCB), these triple-transgenic mice produce BM and spleen grafts with much higher myeloid composition, relative to nontransgenic controls. Shortly after engraftment with UCB, these mice develop a severe, fatal macrophage activation syndrome (MAS) characterized by a progressive drop in rbc numbers, increased reticulocyte counts, decreased rbc half-life, progressive cytopenias, and evidence of chronic inflammation, including elevated human IL-6. The BM becomes strikingly hypocellular, and spleens are significantly enlarged with evidence of extramedullary hematopoiesis and activated macrophages engaged in hemophagocytosis. This manifestation of MAS does not respond to lymphocyte-suppressive therapies such as steroids, i.v. immunoglobulin, or antibody-mediated ablation of human B and T cells, demonstrating a lymphocyte-independent mechanism of action. In contrast, elimination of human myeloid cells using gemtuzumab ozogamicin (anti-CD33) completely reversed the disease. Additionally, the IL-6R antibody tocilizumab delayed progression and prolonged lifespan. This new model of MAS provides an opportunity for investigation of the mechanisms driving this disease and for the testing of directed therapies in a humanized mouse.
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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.