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Paediatric HIV spontaneous controllers (HSCs) are a unique and understudied population with potential to inform alternative treatment options for patients living with HIV. As HSCs are so rare and often not recognised prior to antiretroviral treatment (ART) initiation, it can be difficult for clinicians to optimally manage this group. We describe the diagnosis, history and management of three paediatric HSCs, two girls and a boy who were followed for 2, 1.25 and 10.4 years, respectively, before starting ART. All had low but detectable viral loads throughout follow-up but mostly marginally low CD4:CD8 ratios. The reason for starting ART in all was a gradual tendency to poorer virological control. This case series should assist in recognising paediatric HSCs. Clinical dilemmas arising in the management of paediatric HSCs include arriving at a correct HIV-positive diagnosis, correct diagnosis as an HSC, as well as whether to initiate ART. Decision-making for initiation of ART in paediatric HSCs should be individualised. Factors supporting ART initiation in these patients included increased frequency of viral load blips, increasing detectable viral load, CD4 percentage and CD4:CD8 ratio. Other factors included Hepatitis C serology and highly sensitive C-reactive protein. All three patients ultimately required ART, which supports universal initiation of ART in paediatric HSCs, but further research is required.
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http://dx.doi.org/10.4102/sajid.v37i1.399 | DOI Listing |
Mol Ther Methods Clin Dev
September 2025
Molecular Biology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
X-linked agammaglobulinemia (XLA) is a rare inborn error of immunity caused by loss-of-function mutations in the gene encoding Bruton's tyrosine kinase (BTK). XLA patients lack mature B cells and have negligible antibody levels, leaving them susceptible to recurrent bacterial and chronic viral infections. Autologous hematopoietic stem cell gene therapy with gene-corrected HSC may serve as a promising treatment of XLA; this therapy would provide a one-time cure and would replace lifelong immunoglobulin replacement therapy.
View Article and Find Full Text PDFbioRxiv
August 2025
Department of Cell and Developmental Biology, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hematopoietic stem cells (HSCs), defined as cells that can engraft an adult when transplanted, mature from precursors (pre-HSCs) that differentiate from hemogenic endothelial cells (HECs) in the embryo. Many signaling pathways required to generate the first hematopoietic stem and progenitor cells in the embryo are well-characterized, but how HSCs mature from pre-HSCs is poorly understood. Here we show that "mothers against decapentaplegic homolog 7" (SMAD7), a negative regulator of transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) signaling, is required for pre-HSC to HSC maturation.
View Article and Find Full Text PDFPost-transcriptional RNA modifications, such as N6-methyladenosine (m6A) methylation and adenosine to inosine (A-to-I) editing, are critical regulators of hematopoietic stem cell (HSC) self-renewal and differentiation, yet their precise contributions to malignant transformation are not fully elucidated. In this study, we uncovered the epitranscriptomic landscape caused by knockdown of genes from the methyltransferase (METTL)-family in hematopoietic stem and progenitor cells (HSPCs). We identified both converging and distinct roles of METTL3 and METTL14, known members of the m6A writer complex, as well as orphan gene METTL13.
View Article and Find Full Text PDFElife
September 2025
Department of Pediatrics, Division of Infectious Diseases, and Stem Cells and Regenerative Medicine Center, Baylor College of Medicine and Texas Children's Hospital, Houston, United States.
Human and murine studies reveal that innate immune cells are able to mount enhanced responses to pathogens after primary inflammatory exposure. Innate immune memory has been shown to last for months to years, longer than the lifespan of most innate immune cells. Indeed, long-lived hematopoietic stem and progenitor cells (HSPCs) serve as a cellular reservoir for innate immune memory.
View Article and Find Full Text PDFStem Cells
September 2025
Department of Pediatric Hematology and Oncology, Division of Pediatric Stem Cell Transplantation and Immunology, UKE, Hamburg, Germany.
The sustained production of blood and immune cells is driven by a pool of hematopoietic stem cells (HSCs) and their offspring. Due to the intrinsic heterogeneity of HSCs, the composition of emergent clones changes over time, leading to a reduced clonality in aging mice and humans. Theoretical analyses suggest that clonal conversion rates and clonal complexity depend not only on HSC heterogeneity, but also on additional stress conditions.
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