Evidence map›Paper›PMID 36706754›Full record

Trial reportCell reports. Medicine2023

Severe hematopoietic stem cell inflammation compromises chronic granulomatous disease gene therapy.

Steicy Sobrino, Alessandra Magnani, Michaela Semeraro, Loredana Martignetti, Akira Cortal, Adeline Denis, Chloé Couzin, Capucine Picard, Jacinta Bustamante, Elisa Magrin and 23 more

Registry-linked trialOpen access · goldAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02757911 (A Phase I/II, Non Randomized, Monocentric Open-label Study of Autologous CD34+ Cells Transduced With the G1XCGD Lentiviral Vector in Patients With X-Linked Chronic Granulomatous Disease), which is not on this map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
4.3field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT02757911 phase1 / phase2terminatednot on this map

A Phase I/II, Non Randomized, Monocentric Open-label Study of Autologous CD34+ Cells Transduced With the G1XCGD Lentiviral Vector in Patients With X-Linked Chronic Granulomatous Disease

TypeinterventionalSponsorGenethonRan2013 to 2025Enrolled3ConditionsX-Linked Chronic Granulomatous DiseaseArmsX vivo gene therapy
3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 26 citations in OpenAlex.

  1. Prime Editing for p47The New England journal of medicine · 2026
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  12. Myelodysplasia and transgene inactivation in X-CGD-γ retroviral gene therapy: The usual suspects and new players.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

33 authors at 6 institutions in 3 countries.

Steicy SobrinoHuman Lymphohematopoiesis Laboratory, Université Paris Cité, Imagine Institute, INSERM UMR 1163, Paris, France.
Alessandra MagnaniBiotherapy Department, Necker-Enfants Malades Hospital, AP-HP, Paris, France; Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, AP-HP, INSERM, Paris, France.
Michaela SemeraroClinical Investigation Center CIC 1419, Necker-Enfants Malades Hospital, GH Paris Centre, Université Paris Cité, AP-HP, Paris, France.
Loredana MartignettiClinical Bioinformatics Laboratory, Université Paris Cité, Imagine Institute, INSERM UMR 1163, Paris, France.
Akira CortalClinical Bioinformatics Laboratory, Université Paris Cité, Imagine Institute, INSERM UMR 1163, Paris, France.
Adeline DenisHuman Lymphohematopoiesis Laboratory, Université Paris Cité, Imagine Institute, INSERM UMR 1163, Paris, France.
Chloé CouzinBiotherapy Department, Necker-Enfants Malades Hospital, AP-HP, Paris, France; Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, AP-HP, INSERM, Paris, France.
Capucine PicardStudy Center for Primary Immunodeficiencies, Necker-Enfants Malades Hospital, AP-HP, Université Paris Cité, Paris, France; Lymphocyte Activation and Susceptibility to EBV Infection Laboratory, INSERM UMR 1163, Imagine Institute, Paris, France; Centre de Références des Déficits Immunitaires Héréditaires (CEREDIH), Necker-Enfants Malades Hospital, AP-HP, Paris, France.
Jacinta BustamanteStudy Center for Primary Immunodeficiencies, Necker-Enfants Malades Hospital, AP-HP, Université Paris Cité, Paris, France; Human Genetics of Infectious Diseases Laboratory, Université Paris Cité, Imagine Institute, INSERM UMR 1163, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
Elisa MagrinBiotherapy Department, Necker-Enfants Malades Hospital, AP-HP, Paris, France; Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, AP-HP, INSERM, Paris, France.
Laure JosephBiotherapy Department, Necker-Enfants Malades Hospital, AP-HP, Paris, France.
Cécile RoudautBiotherapy Department, Necker-Enfants Malades Hospital, AP-HP, Paris, France; Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, AP-HP, INSERM, Paris, France.
Aurélie GabrionBiotherapy Department, Necker-Enfants Malades Hospital, AP-HP, Paris, France; Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, AP-HP, INSERM, Paris, France.
Tayebeh SoheiliHuman Lymphohematopoiesis Laboratory, Université Paris Cité, Imagine Institute, INSERM UMR 1163, Paris, France.
Corinne CordierPlateforme de Cytométrie en Flux, Structure Fédérative de Recherche Necker, INSERM US24-CNRS UAR3633, Paris, France.
Olivier LortholaryNecker-Pasteur Center for Infectious Diseases and Tropical Medicine, Necker-Enfants Malades Hospital, AP-HP, Université Paris Cité, Imagine Institute, Paris, France.
François LefrereBiotherapy Department, Necker-Enfants Malades Hospital, AP-HP, Paris, France; Department of Adult Hematology, Necker-Enfants Malades Hospital, AP-HP, Paris, France.
Frédéric Rieux-LaucatImmunogenetics of Pediatric Autoimmune Diseases Laboratory, Université Paris Cité, Imagine Institute, INSERM UMR 1163, Paris, France.
Jean-Laurent CasanovaHuman Genetics of Infectious Diseases Laboratory, Université Paris Cité, Imagine Institute, INSERM UMR 1163, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
Sylvain BodardDepartment of Adult Radiology, Necker Enfants-Malades Hospital, AP-HP, Université Paris Cité, Paris, France; Laboratoire d'Imagerie Biomédicale, LIB, Sorbonne Université, CNRS, INSERM, Paris, France.
Nathalie BoddaertDépartement de Radiologie Pédiatrique, INSERM UMR 1163 and UMR 1299, Imagine Institute, AP-HP, Necker-Enfants Malades Hospital, Paris, France.
Adrian J ThrasherUCL Great Ormond Street Institute of Child Health, London, UK; Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Fabien TouzotBiotherapy Department, Necker-Enfants Malades Hospital, AP-HP, Paris, France; Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, AP-HP, INSERM, Paris, France.
Sophie TaqueCHU de Rennes, Département de Pédiatrie, Rennes, France.
Felipe SuarezNecker-Pasteur Center for Infectious Diseases and Tropical Medicine, Necker-Enfants Malades Hospital, AP-HP, Université Paris Cité, Imagine Institute, Paris, France; Imagine Institute, Université Paris Cité, Paris, France.
Ambroise MarcaisNecker-Pasteur Center for Infectious Diseases and Tropical Medicine, Necker-Enfants Malades Hospital, AP-HP, Université Paris Cité, Imagine Institute, Paris, France.
Agathe GuillouxMathematics and Modelization Laboratory, CNRS, Université Paris-Saclay, Université d'Evry, Evry, France.
Chantal Lagresle-PeyrouHuman Lymphohematopoiesis Laboratory, Université Paris Cité, Imagine Institute, INSERM UMR 1163, Paris, France; Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, AP-HP, INSERM, Paris, France.
Anne GalyGenethon, Evry-Courcouronnes, France; Université Paris-Saclay, University Evry, Inserm, Genethon (UMR_S951), Evry-Courcouronnes, France.
Antonio RausellClinical Bioinformatics Laboratory, Université Paris Cité, Imagine Institute, INSERM UMR 1163, Paris, France; Service de Médecine Génomique des Maladies Rares, AP-HP, Necker-Enfants Malades Hospital, Paris, France.
Stephane BlancheDepartment of Pediatric Immunology, Hematology, and Rheumatology, Necker-Enfants Malades Hospital, AP-HP, Paris, France.
Marina CavazzanaBiotherapy Department, Necker-Enfants Malades Hospital, AP-HP, Paris, France; Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, AP-HP, INSERM, Paris, France; Imagine Institute, Université Paris Cité, Paris, France. Electronic address: m.cavazzana@aphp.fr.
Emmanuelle SixHuman Lymphohematopoiesis Laboratory, Université Paris Cité, Imagine Institute, INSERM UMR 1163, Paris, France.
Hôpital Necker-Enfants Malades · FRInserm · FRCentre National de la Recherche Scientifique · FRDélégation Paris 5 · FRCentre Hospitalier Universitaire de Rennes · FRGreat Ormond Street Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

X-linked chronic granulomatous disease (CGD) is associated with defective phagocytosis, life-threatening infections, and inflammatory complications. We performed a clinical trial of lentivirus-based gene therapy in four patients (NCT02757911). Two patients show stable engraftment and clinical benefits, whereas the other two have progressively lost gene-corrected cells. Single-cell transcriptomic analysis reveals a significantly lower frequency of hematopoietic stem cells (HSCs) in CGD patients, especially in the two patients with defective engraftment. These two present a profound change in HSC status, a high interferon score, and elevated myeloid progenitor frequency. We use elastic-net logistic regression to identify a set of 51 interferon genes and transcription factors that predict the failure of HSC engraftment. In one patient, an aberrant HSC state with elevated CEBPβ expression drives HSC exhaustion, as demonstrated by low repopulation in a xenotransplantation model. Targeted treatments to protect HSCs, coupled to targeted gene expression screening, might improve clinical outcomes in CGD.

Indexed as

Granulomatous Disease, ChronicHematopoietic Stem Cell TransplantationGenetic TherapyHematopoietic Stem CellsHumansInflammationInterferonsInterferonschronic granulomatous diseasechronic inflammationexhaustiongene therapyhematopoietic stem cellsinborn errors of immunitymachine learningsingle-cell RNA-seq

Identifiers

PMID36706754
PMCPMC9975109
OpenAlexW4318392222

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.