ArticleGenome medicine2018
T cell dynamics and response of the microbiota after gene therapy to treat X-linked severe combined immunodeficiency.
Article in Genome medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 21 papers.
What it found
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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.
Multi-site Phase I/II Trial Evaluating the Treatment of SCID-X1 Patients With Retrovirus-mediated Gene Transfer
Gene Therapy for SCID-X1 Using a Self-inactivating (SIN) Gammaretroviral Vector
Protocol No. 2 of Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID-X1) Using a Self Retroviral Vector - SCID2
Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- The next-generation DNA vaccine platforms and delivery systems: advances, challenges and prospects.Frontiers in immunology · 2024Review
- Gene therapy for inborn errors of immunity: past, present and future.Nature reviews. Immunology · 2023Review
- Homology-Directed-Repair-Based Genome Editing in HSPCs for the Treatment of Inborn Errors of Immunity and Blood Disorders.Pharmaceutics · 2023Review
- Microbiome and Its Dysbiosis in Inborn Errors of Immunity.Pathogens (Basel, Switzerland) · 2023Review
- Treg-associated monogenic autoimmune disorders and gut microbial dysbiosis.Pediatric research · 2022Review
- Inborn errors of immunity and related microbiome.Frontiers in immunology · 2022Review
- Development and clinical translation ofComputational and structural biotechnology journal · 2022Review
- The human virome: assembly, composition and host interactions.Nature reviews. Microbiology · 2021Review
- Rengasvirus, a Circular Replication-Associated Protein-Encoding Single-Stranded DNA Virus-Related Genome That Is a Common Contaminant in Metagenomic Data.Microbiology resource announcements · 2021Article
- Interrogation of clonal tracking data usingNature computational science · 2021Article
- Gut Microbiota-Host Interactions in Inborn Errors of Immunity.International journal of molecular sciences · 2021Review
- Dysregulation of the Intestinal Microbiome in Patients With Haploinsufficiency of A20.Frontiers in cellular and infection microbiology · 2021Article
- Hemophagocytic syndrome associated with Mycobacterium bovis in a patient with X-SCID: a case report.BMC infectious diseases · 2020Article
- Long-term robustness of a T-cell system emerging from somatic rescue of a genetic block in T-cell development.EBioMedicine · 2020Article
- Adeno-Associated Virus-Based Gene Therapy for Lifelong Correction of Genetic Disease.Human gene therapy · 2020Review
- Preclinical Development of Autologous Hematopoietic Stem Cell-Based Gene Therapy for Immune Deficiencies: A Journey from Mouse Cage to Bed Side.Pharmaceutics · 2020Review
- Gene therapy for severe combined immunodeficiencies and beyond.The Journal of experimental medicine · 2020Review
- Immune Reconstitution After Gene Therapy Approaches in Patients With X-Linked Severe Combined Immunodeficiency Disease.Frontiers in immunology · 2020Review
- Somatic genetic rescue in Mendelian haematopoietic diseases.Nature reviews. Genetics · 2019Review
- Article
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundMutation of the IL2RG gene results in a form of severe combined immune deficiency (SCID-X1), which has been treated successfully with hematopoietic stem cell gene therapy. SCID-X1 gene therapy results in reconstitution of the previously lacking T cell compartment, allowing analysis of the roles of T cell immunity in humans by comparing before and after gene correction.
methodsHere we interrogate T cell reconstitution using four forms of high throughput analysis. (1) Estimation of the numbers of transduced progenitor cells by monitoring unique positions of integration of the therapeutic gene transfer vector. (2) Estimation of T cell population structure by sequencing of the recombined T cell receptor (TCR) beta locus. (3) Metagenomic analysis of microbial populations in oropharyngeal, nasopharyngeal, and gut samples. (4) Metagenomic analysis of viral populations in gut samples.
resultsComparison of progenitor and mature T cell populations allowed estimation of a minimum number of cell divisions needed to generate the observed populations. Analysis of microbial populations showed the effects of immune reconstitution, including normalization of gut microbiota and clearance of viral infections. Metagenomic analysis revealed enrichment of genes for antibiotic resistance in gene-corrected subjects relative to healthy controls, likely a result of higher healthcare exposure.
conclusionsThis multi-omic approach enables the characterization of multiple effects of SCID-X1 gene therapy, including T cell repertoire reconstitution, estimation of numbers of cell divisions between progenitors and daughter T cells, normalization of the microbiome, clearance of microbial pathogens, and modulations in antibiotic resistance gene levels. Together, these results quantify several aspects of the long-term efficacy of gene therapy for SCID-X1. This study includes data from ClinicalTrials.gov numbers NCT01410019, NCT01175239, and NCT01129544.
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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.