ArticleInflammatory bowel diseases2020
The Combination of Patient Profiling and Preclinical Studies in a Mouse Model Based on NOD/Scid IL2Rγ null Mice Reconstituted With Peripheral Blood Mononuclear Cells From Patients With Ulcerative Colitis May Lead to Stratification of Patients for Treatment With Adalimumab.
Article in Inflammatory bowel diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Murine and Humanized Mouse Models in Autoimmune Disease Research and Therapeutics Development.Biology · 2026Review
- Advancement of humanized mice and leading applications in immunological disease models.Inflammation and regeneration · 2026Review
- Validation of a model of rheumatoid arthritis using mice reconstituted with patient peripheral blood mononuclear cells.Disease models & mechanisms · 2025Article
- Effect of Anti-TNF Monoclonal Antibody on Enteric Neurons and Enteric Glial Cells in Experimental Colitis.Digestive diseases and sciences · 2025Article
- NOD/Scid IL2RγJID innovations : skin science from molecules to population health · 2024Article
- Humanized NSG Mouse Models as a Preclinical Tool for Translational Research in Inflammatory Bowel Diseases.International journal of molecular sciences · 2023Article
- NOD/scid IL-2RγImmunity, inflammation and disease · 2021Article
- Suppressing Kv1.3 Ion Channel Activity with a Novel Small Molecule Inhibitor Ameliorates Inflammation in a Humanised Mouse Model of Ulcerative Colitis.Journal of Crohn's & colitis · 2021Article
- The PI3K pathway as a therapeutic intervention point in inflammatory bowel disease.Immunity, inflammation and disease · 2021Article
- Review
- Autoantibodies as diagnostic markers and potential drivers of inflammation in ulcerative colitis.PloS one · 2020Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
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Abstract
backgroundTo date, responsiveness to tumor necrosis factor alpha inhibitors in ulcerative colitis (UC) patients is not predictable. This is partially due to a lack of understanding of the underlying inflammatory processes. The aim of this study was to identify immunological subgroups of patients with UC and to test responsiveness to adalimumab in these subgroups in the mouse model of ulcerative colitis (UC), which is based on NOD/scid IL-2Rγ null (NSG) mice reconstituted with peripheral blood mononuclear cells (PBMCs; NSG-UC).
methodsThe immunological profiles of 40 UC patients and 16 non-UC donors were determined by flow cytometric analysis of PBMCs in a snapshot and longitudinal study and analyzed by principal component, orthogonal partial least square discrimination (oPLS-DA), and hierarchical clustering analysis. NSG mice were reconstituted 5 times at consecutive time points with PBMCs from a single donor and were analyzed for frequencies of human leukocytes and histological phenotype. The response to adalimumab of 2 identified subgroups was tested in the NSG-UC model. We used the clinical, colon, and histological score, serum levels of glutamic and aspartic acid, and IL-6 and IL-1ß. Response was analyzed by oPLS-DA.
resultsAnalysis revealed a distinction between UC and non-UC donors. Hierarchical clustering identified 2 major subgroups in UC patients. Group I was characterized by TH17 and M1 monocytes, group II by TH2/TH1, and switched B cells. These subgroups reflect the dynamics of inflammation as patients. NSG-UC mice achieved an immunological phenotype reflecting the patient's immunological phenotype. oPLS-DA revealed that NSG-UC mice reconstituted with PBMCs from group II responded better to adalimumab.
conclusionsThe combination of profiling and testing of therapeutics in the NSG-UC model may lead to individualized and phase-dependent therapies.
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