Publications by authors named "Ben K Margetts"
Article Synopsis
- Deficiency of the enzyme adenosine deaminase (ADA) leads to severe combined immunodeficiency (SCID) due to toxic metabolite buildup, affecting T cell development and function in both humans and mouse models.
- Treatments like enzyme replacement therapy (ERT) using pegylated bovine ADA (PEG-ADA) can improve survival but often result in low T and B cell numbers, indicating suboptimal immune recovery.
- Research shows that despite weekly PEG-ADA treatment in ADA-SCID mice, thymus cellularity is reduced, and thymocyte development is stalled, suggesting that ERT does not fully address the underlying metabolic and immunological issues caused by ADA deficiency.
A recent surge in human mastadenovirus (HAdV) cases, including five deaths, amongst a haematopoietic stem cell transplant population led us to use whole genome sequencing (WGS) to investigate. We compared sequences from 37 patients collected over a 20-month period with sequences from GenBank and our own database of HAdVs. Maximum likelihood trees and pairwise differences were used to evaluate genotypic relationships, paired with the epidemiological data from routine infection prevention and control (IPC) records and hospital activity data.
View Article and Find Full Text PDFSpectratyping assays are well recognized as the clinical gold standard for assessing the T cell receptor (TCR) repertoire in haematopoietic stem cell transplant (HSCT) recipients. These assays use length distributions of the hyper variable complementarity-determining region 3 (CDR3) to characterize a patient's T cell immune reconstitution post-transplant. However, whilst useful, TCR spectratyping is notably limited by its resolution, with the technique unable to provide data on the individual clonotypes present in a sample.
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- Adenoviruses pose a risk to immunocompromised patients, and traditional serotyping methods fall short in tracking transmissions in healthcare settings.* -
- The study implemented a whole-genome sequencing (WGS) approach to analyze adenovirus samples from patients over a 5-year period, successfully recovering sequences from most samples.* -
- WGS revealed important insights into transmission patterns, including connections between cases and the presence of mixed infections, demonstrating its advantages over conventional genotyping in understanding adenovirus spread.*
Human cytomegalovirus (HCMV) is a significant pathogen in immunocompromised individuals, with the potential to cause fatal pneumonitis and colitis, as well as increasing the risk of organ rejection in transplant patients. With the advent of new anti-HCMV drugs there is therefore considerable interest in using virus sequence data to monitor emerging resistance to antiviral drugs in HCMV viraemia and disease, including the identification of putative new mutations. We used target-enrichment to deep sequence HCMV DNA from 11 immunosuppressed pediatric patients receiving single or combination anti-HCMV treatment, serially sampled over 1-27 weeks.
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