Severe hematopoietic stem cell inflammation compromises chronic granulomatous disease gene therapy (Single Cell)

ABSTRACT: X-linked chronic granulomatous disease (CGD, caused by CYBB gene mutations) 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 showed stable engraftment and clinical benefits, whereas the other two progressively lost gene-corrected cells. Single-cell transcriptomic analysis revealed a significantly lower frequency of the most immature hematopoietic stem cells (HSCs) in CGD patients, especially in the two patients with defective engraftment. The latter presented a profound change in HSCs status, a high interferon score, and elevated myeloid progenitor frequency. We used elastic-net logistic regression to identify a set of 51 interfe

ORGANISM(S): Homo sapiens (human)

SUBMITTER:  

PROVIDER: S-BSST959 | biostudies-other |

REPOSITORIES: biostudies-other