Biology subjects

Eason, J.

Publications and source records attributed to Eason, J..

4 recordsLinked to original sources

bioRxiv2025

Comparative Landscape of Small RNAs in Tissue and Liquid Biopsies for Liver Transplant Outcomes

BackgroundIschemia-reperfusion injury (IRI) is an inevitable consequence of liver transplantation, arising during donor organ procurement and reoxygenation. Severe IRI is a leading contributor to early allograft dysfunction (EAD), a post-transplant complication associated with reduced graft survival. Current postoperative biomarkers provide limited time for intervention, highlighting a need to identify preoperative biomarkers of IRI. Meanwhile, tRNA fragments (tRFs) have emerged as novel biomarkers in various diseases but remain unexplored in the context of liver transplant. ResultsWe performed small RNA sequencing on 96 paired donor liver biopsies from 48 patients to investigate IRI-associated transcript changes. In parallel, 161 donor liver perfusates were analyzed as a non-invasive surrogate for tissue. Across samples, microRNAs (miRNAs) and tRFs were the most abundant. Perfusate expression strongly correlated with biopsies, supporting their value as a non-invasive source of small RNAs. Comparison between post-reperfusion and pre-implantation biopsies revealed that IRI reprogrammed tRF expression. Stratification by clinical outcome showed that patients who developed EAD exhibited specific small RNA signatures in both biopsy and perfusate. Receiver operating characteristic (ROC) analysis revealed a miRNA-based model that achieved an AUC of 0.772, outperforming donor risk index alone (AUC = 0.665), representing a 10.7% increase in discriminative capacity. ConclusionsThese results are the first to establish tRFs as IRI-responsive biomolecules abundant in both donor liver tissue and non-invasive perfusate. In particular, various small RNAs emerged as promising candidate biomarkers for early detection of EAD. These results lay the foundation to further investigate the prognostic utility of tRFs/miRNAs in liver transplantation.

genomics↗

bioRxiv2025

Adaptive-like NK cell responses to influenza correlate with humoral immunity and are influenced by age and sex

Influenza remains a global health threat, infecting approximately one billion people annually and causing significant mortality, particularly among older adults. While hemagglutination inhibition (HAI) antibody titers are a standard correlate of immunity against influenza, they do not reliably predict protection in high-risk populations. Using multiomic single-cell profiling, we identified a distinct subset of adaptive-like NK cells that respond to influenza antigen, predominantly in younger females. These TNFSF10+LGALS9+ NK cells exhibit features of adaptive NK cells but lack classical cytomegalovirus-driven markers observed in previous studies. Notably, their increased frequency correlates with high pre-existing HAI titers, suggesting a link between adaptive-like NK responses and humoral immunity. Together, our findings identify an NK subset influenced by age and sex that may contribute to influenza protection, expanding the known diversity of adaptive-like NK cells. These insights could inform future vaccine strategies, particularly for aging populations, by integrating NK responses into assessments of vaccine efficacy.

immunology↗

bioRxiv2025

Antiviral CD4+ T and myeloid cell responses to influenza vaccines are attenuated in older adults

Recent influenza vaccine formulations have improved the magnitude of B-cell antibody responses in older adults; however, older adults remain significantly at risk for severe influenza-related illness. Although antibodies are an important metric of vaccine effectiveness, they only represent one aspect of the immune response. In this study, we combined in vitro and ex vivo assays with human samples to investigate B, CD4+ T, and myeloid cell responses to influenza vaccine antigens. We found that older adults mounted equivalent antibody titers to younger adults but had fewer influenza-specific CD4+ T cells and reduced antiviral-associated T helper cell populations. Single-cell transcriptomics revealed that older adults had attenuated interferon transcriptional signatures in T helper and myeloid cell subsets. These data suggest that with aging, transcriptional programming alterations in myeloid cells contribute to reduced antiviral T cell responses, and formulating vaccines tailored to myeloid responses is necessary to improve outcomes in older adults.

immunology↗

bioRxiv2022

The PREGCARE study: Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation

Next-generation sequencing has led to a dramatic improvement in molecular diagnoses of serious pediatric disorders caused by apparently de novo mutations (DNMs); by contrast, clinicians ability to counsel the parents about the risk of recurrence in a future child has lagged behind. Owing to the possibility that one of the parents could be mosaic in their germline, a recurrence risk of 1-2% is frequently quoted, but for any specific couple, this figure is usually incorrect. We present a systematic approach to providing individualized recurrence risk stratification, by combining deep-sequencing of multiple tissues in the mother-father-child trio with haplotyping to determine the parental origin of the DNM. In the first 58 couples analysed (total of 59 DNMs in 49 different genes), the risk for 35 (59%) DNMs was decreased below 0.1% but for 6 (10%) couples it was increased owing to parental mosaicism - that could be quantified in semen (recurrence risks of 5.6-12.1%) for the paternal cases. Deep-sequencing of the DNM efficiently identifies couples at greatest risk for recurrence and may qualify them for additional reproductive technologies. Haplotyping can further reassure many other couples that their recurrence risk is very low, but its implementation is more technically challenging and will require better understanding of how couples respond to information that reduces their risks.

genetics↗