Development of antigen-specific memory upon pathogen exposure is a hallmark of the adaptive immune system. While natural killer (NK) cells are considered part of the innate immune system, humans exposed to the chronic viral pathogen cytomegalovirus (CMV) often possess a distinct NK cell population lacking in individuals who have not been exposed, termed "adaptive" NK cells. To identify the "naïve" population from which this "memory" population derives, we performed phenotypic, transcriptional, and functional profiling of NK cell subsets.
View Article and Find Full Text PDFBackground: Despite adherence to reprocessing protocols, duodenoscopes frequently remain contaminated, highlighting significant knowledge gaps in reprocessing efficiency.
Aim: To identify risk factors in duodenoscope reprocessing procedures affecting contamination rates.
Methods: Cultures from Pentax ED34-i10T2 duodenoscopes collected between February 2022 and December 2023 were included.
Background And Aims: Periodic duodenoscope cultures are essential to timely detect contamination, but their sensitivity remains unknown. This study aims to determine the sensitivity of duodenoscope cultures and to estimate the prevalence of contaminated duodenoscope use.
Methods: We combined duodenoscope microbiologic surveillance data from March 2015 to June 2022 with usage data to evaluate patient exposure to duodenoscopes contaminated with microorganisms of gut or oral origin (MGO).
Reprocessing reusable endoscopes is challenging due to their non-sterilizable nature. Disinfection has been shown to have a significant risk of failure with serious consequences. Single-use endoscopes can eliminate contamination risk and reduce workflow delays caused by reprocessing.
View Article and Find Full Text PDFBackground: Duodenoscope-associated infections (DAIs) are exogenous infections resulting from the use of contaminated duodenoscopes. Though numerous outbreaks of DAI have involved multidrug-resistant micro-organisms (MDROs), outbreaks involving non-MDROs are also likely to occur. Detection challenges arise as these infections often resolve before culture or because causative strains are not retained for comparison with duodenoscope strains.
View Article and Find Full Text PDFObjective: Contaminated duodenoscopes caused several hospital outbreaks. Despite efforts to reduce contamination rates, 15% of patient-ready duodenoscopes are still contaminated with gastrointestinal microorganisms. This study aimed to provide an overview of duodenoscope contamination over time, identify risk factors and study the effects of implemented interventions.
View Article and Find Full Text PDFBackground: Current duodenoscope reprocessing protocols are insufficient to prevent contamination and require adaptations to prevent endoscopy-associated infections (EAIs). This study aimed to investigate the effect of a new endoscope cleaning brush on the contamination rate of ready-to-use duodenoscopes.
Methods: This retrospective before-and-after intervention study collected duodenoscope surveillance culture results from March 2018 to June 2022.
Development of antigen-specific memory upon pathogen exposure is a hallmark of the adaptive immune system. While natural killer (NK) cells are considered part of the innate immune system, humans exposed to the chronic viral pathogen cytomegalovirus (CMV) often possess a distinct NK cell population lacking in individuals who have not been exposed, termed "adaptive" NK cells. To identify the "naïve" population from which this "memory" population derives, we performed phenotypic, transcriptional, and functional profiling of NK cell subsets.
View Article and Find Full Text PDFBackground: Malaria in pregnancy (MIP) causes higher morbidity in primigravid compared to multigravid women; however, the correlates and mechanisms underlying this gravidity-dependent protection remain incompletely understood. We aimed to compare the cellular immune response between primigravid and multigravid women living in a malaria-endemic region and assess for correlates of protection against MIP.
Methods: We characterised the second trimester cellular immune response among 203 primigravid and multigravid pregnant women enrolled in two clinical trials of chemoprevention in eastern Uganda, utilizing RNA sequencing, flow cytometry, and functional assays.
T cells are a critical component of the response to SARS-CoV-2, but their kinetics after infection and vaccination are insufficiently understood. Using "spheromer" peptide-MHC multimer reagents, we analyzed healthy subjects receiving two doses of the Pfizer/BioNTech BNT162b2 vaccine. Vaccination resulted in robust spike-specific TÂ cell responses for the dominant CD4 (HLA-DRB115:01/S191) and CD8 (HLA-A02/S691) TÂ cell epitopes.
View Article and Find Full Text PDFBackground And Aims: The clinical course of patients with liver cirrhosis and adherence to hepatocellular carcinoma (HCC) screening guidelines are not well studied in the Netherlands. We investigated this and potential risk factors for decompensation and transplant-free survival (TFS) in a large regional cohort.
Methods: We performed a retrospective cohort study of patients with confirmed liver cirrhosis in Amsterdam, the Netherlands.
Natural killer (NK) cells likely play an important role in immunity to malaria, but the effect of repeated malaria on NK cell responses remains unclear. Here, we comprehensively profiled the NK cell response in a cohort of 264 Ugandan children. Repeated malaria exposure was associated with expansion of an atypical, CD56 population of NK cells that differed transcriptionally, epigenetically, and phenotypically from CD56 NK cells, including decreased expression of PLZF and the Fc receptor γ-chain, increased histone methylation, and increased protein expression of LAG-3, KIR, and LILRB1.
View Article and Find Full Text PDFBackground: The great majority of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infections are mild and uncomplicated, but some individuals with initially mild COVID-19 progressively develop more severe symptoms. Furthermore, there is substantial heterogeneity in SARS-CoV-2-specific memory immune responses following infection. There remains a critical need to identify host immune biomarkers predictive of clinical and immunological outcomes in SARS-CoV-2-infected patients.
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4 T cells are likely important in immunity against coronavirus 2019 (COVID-19), but our understanding of CD4 longitudinal dynamics following infection and of specific features that correlate with the maintenance of neutralizing antibodies remains limited. Here, we characterize SARS-CoV-2-specific CD4 T cells in a longitudinal cohort of 109 COVID-19 outpatients enrolled during acute infection. The quality of the SARS-CoV-2-specific CD4 response shifts from cells producing interferon gamma (IFNγ) to tumor necrosis factor alpha (TNF-α) from 5 days to 4 months post-enrollment, with IFNγIL-21TNF-α CD4 T cells the predominant population detected at later time points.
View Article and Find Full Text PDFHLA-B allotypes exhibiting the Bw4 epitope trigger variable inhibitory signaling of KIR3DL1 receptor types, where strong inhibitory HLA-B and KIR3DL1 allele combinations are associated with increased risk for relapse of acute myelogenous leukemia (AML) following allogeneic hematopoietic cell transplantation (HCT). Several HLA-A allotypes also exhibit the Bw4 epitope. Studies with natural killer (NK) cell clones have demonstrated NK inhibition via KIR3DL1 by HLA-A Bw4+ allotypes, but did not delineate strengths of inhibition or hierarchies of NK education.
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