9 results on '"Leavis, Helen L"'
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2. Lipoteichoic acid synthesis inhibition in combination with antibiotics abrogates growth of multidrug-resistant Enterococcus faecium
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Paganelli, Fernanda L., van de Kamer, Tim, Brouwer, Ellen C., Leavis, Helen L., Woodford, Neil, Bonten, Marc J.M., Willems, Rob J.L., and Hendrickx, Antoni P.A.
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- 2017
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3. Immunogenicity of the mRNA-1273 COVID-19 vaccine in adult patients with inborn errors of immunity.
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van Leeuwen, Leanne P.M., GeurtsvanKessel, Corine H., Ellerbroek, Pauline M., de Bree, Godelieve J., Potjewijd, Judith, Rutgers, Abraham, Jolink, Hetty, van de Veerdonk, Frank, van Gorp, Eric C.M., de Wilt, Faye, Bogers, Susanne, Gommers, Lennert, Geers, Daryl, Bruns, Anke H.W., Leavis, Helen L., van Haga, Jelle W., Lemkes, Bregtje A., van der Veen, Annelou, de Kruijf-Bazen, S.F.J., and van Paassen, Pieter
- Abstract
Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective vaccination against COVID-19 is therefore of great importance in this group, but little is known about the immunogenicity of COVID-19 vaccines in these patients. We sought to study humoral and cellular immune responses after mRNA-1273 COVID-19 vaccination in adult patients with IEI. In a prospective, controlled, multicenter study, 505 patients with IEI (common variable immunodeficiency [CVID], isolated or undefined antibody deficiencies, X-linked agammaglobulinemia, combined B- and T-cell immunodeficiency, phagocyte defects) and 192 controls were included. All participants received 2 doses of the mRNA-1273 COVID-19 vaccine. Levels of severe acute respiratory syndrome coronavirus-2–specific binding antibodies, neutralizing antibodies, and T-cell responses were assessed at baseline, 28 days after first vaccination, and 28 days after second vaccination. Seroconversion rates in patients with clinically mild antibody deficiencies and phagocyte defects were similar to those in healthy controls, but seroconversion rates in patients with more severe IEI, such as CVID and combined B- and T-cell immunodeficiency, were lower. Binding antibody titers correlated well to the presence of neutralizing antibodies. T-cell responses were comparable to those in controls in all IEI cohorts, with the exception of patients with CVID. The presence of noninfectious complications and the use of immunosuppressive drugs in patients with CVID were negatively correlated with the antibody response. COVID-19 vaccination with mRNA-1273 was immunogenic in mild antibody deficiencies and phagocyte defects and in most patients with combined B- and T-cell immunodeficiency and CVID. Lowest response was detected in patients with X-linked agammaglobulinemia and in patients with CVID with noninfectious complications. The assessment of longevity of immune responses in these vulnerable patient groups will guide decision making for additional vaccinations. [ABSTRACT FROM AUTHOR]
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- 2022
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4. Adult-onset autoinflammation caused by somatic mutations in UBA1: A Dutch case series of patients with VEXAS.
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van der Made, Caspar I., Potjewijd, Judith, Hoogstins, Annemiek, Willems, Huub P.J., Kwakernaak, Arjan J., de Sevaux, Ruud G.L., van Daele, Paul L.A., Simons, Annet, Heijstek, Marloes, Beck, David B., Netea, Mihai G., van Paassen, Pieter, Elizabeth Hak, A., van der Veken, Lars T., van Gijn, Marielle E., Hoischen, Alexander, van de Veerdonk, Frank L., Leavis, Helen L., and Rutgers, Abraham
- Abstract
A novel autoinflammatory syndrome was recently described in male patients who harbored somatic mutations in the X-chromosomal UBA1 gene. These patients were characterized by adult-onset, treatment-refractory inflammation with fever, cytopenia, dysplastic bone marrow, vacuoles in myeloid and erythroid progenitor cells, cutaneous and pulmonary inflammation, chondritis, and vasculitis, which is abbreviated as VEXAS. This study aimed to (retrospectively) diagnose VEXAS in patients who had previously been registered as having unclassified autoinflammation. We furthermore aimed to describe clinical experiences with this multifaceted, complex disease. A systematic reanalysis of whole-exome sequencing data from a cohort of undiagnosed patients with autoinflammation from academic hospitals in The Netherlands was performed. When no sequencing data were available, targeted Sanger sequencing was applied in cases with high clinical suspicion of VEXAS. A total of 12 male patients who carried mutations in UBA1 were identified. These patients presented with adult-onset (mean age 67 years, range 47-79 years) autoinflammation with systemic symptoms, elevated inflammatory parameters, and multiorgan involvement, most typically involving the skin and bone marrow. Novel features of VEXAS included interstitial nephritis, cardiac involvement, stroke, and intestinal perforation related to treatment with tocilizumab. Although many types of treatment were initiated, most patients became treatment-refractory, with a high mortality rate of 50%. VEXAS should be considered in the differential diagnosis of males with adult-onset autoinflammation characterized by systemic symptoms and multiorgan involvement. Early diagnosis can prevent unnecessary diagnostic procedures and provide better prognostic information and more suitable treatment options, including stem cell transplantation. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Identification of high-risk enterococcal clonal complexes: global dispersion and antibiotic resistance
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Leavis, Helen L, Bonten, Marc JM, and Willems, Rob JL
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ENTEROCOCCUS , *VANCOMYCIN resistance , *HOSPITALS , *EPIDEMICS - Abstract
Vancomycin-resistant Enterococcus faecium spread dramatically in hospital settings in the USA in the 1990s and reached endemicity at the turn of the century. Similarly, rising prevalence rates are currently observed in several European countries, with prevalence rates of greater than 10% reported in seven of these. On the basis of multilocus sequence typing (MLST), the population structure of E. faecium was elucidated and the existence of a distinct high-risk enterococcal clonal complex, designated clonal complex-17 (CC17), which is associated with the majority of hospital outbreaks and clinical infections in five continents, was revealed. This complex is correlated with ampicillin and quinolone resistance and with the presence of a putative pathogenicity island. Preliminary MLST data suggest that similar hospital-adapted complexes might also exist in E. faecalis. [Copyright &y& Elsevier]
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- 2006
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6. Optimizing future treatment of enterococcal infections: attacking the biofilm?
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Paganelli, Fernanda L., Willems, Rob J., and Leavis, Helen L.
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ENTEROCOCCUS faecalis , *ENTEROCOCCAL infections , *BIOFILMS , *ANTIBIOTICS , *PHAGOCYTOSIS , *GENETIC regulation , *PHARMACOLOGY , *ARTIFICIAL implants , *THERAPEUTICS - Abstract
Enterococcus faecalis and Enterococcus faecium are among the leading causative agents of nosocomial infections and are infamous for their resistance to many antibiotics. They cause difficult-to-treat infections, often originating from biofilm-mediated infections associated with implanted medical devices or endocarditis. Biofilms protect bacteria against antibiotics and phagocytosis, and physical removal of devices or infected tissue is often needed but is frequently not possible. Currently there are no clinically available compounds that disassemble biofilms. In this review we discuss all known structural and regulatory genes involved in enterococcal biofilm formation, the compounds directed against biofilm formation that have been studied, and potentially useful targets for future drugs to treat enterococcal biofilm-associated infections. [ABSTRACT FROM AUTHOR]
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- 2012
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7. Targeted Sequence Capture Metagenomics (ViroCap) to Detect Viruses in Stool Samples of Hematopoietic Stem Cell Transplantation Patients.
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Jansen, Suze A., Nijhuis, Wouter, Leavis, Helen L., Riezebos-Brilman, Annelies, Lindemans, Caroline A., and Schuurman, Rob
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HEMATOPOIETIC stem cell transplantation , *CHLOROPLAST DNA , *METAGENOMICS , *DNA viruses , *VIRUSES , *HEMATOPOIETIC system - Abstract
Gastro-intestinal (GI) symptoms in pediatric allogeneic hematopoietic stem cell transplantation (HSCT) patients are common and may be caused by viruses, Graft-Versus-Host-Disease (GVHD) or both. Currently, little is known about the GI viriome in SCT patients, hindering the study of the pathogenicity and role in GVHD. We used ViroCap, a viral target enrichment method, in combination with Next Generation Sequencing (NGS) to detect viruses in stool samples of HSCT patients and compared to PCR results. Using ViroCap, nucleic acid of a broad range of RNA and DNA viruses infecting vertebrate hosts was enriched in banked stool samples of HSCT patients. Upon enrichment, samples were sequenced by NGS on an Illumina MiSeq system and detected viral sequences were analyzed using the automated Genome Detective pipeline (GD) and/or directly aligned (DA) to a reference sequence of a specific virus, using Genious software. Where possible, presence of newly detected viral pathogens was confirmed by virus-specific qPCR. Stool samples of 11 patients, age range 1-17, that had undergone HSCT for a variety of indications were selected for ViroCap analysis. All selected patients suffered from GI-symptoms. Ten were diagnosed with grade I-IV GI-GVHD according to consensus guidelines. In 6 samples adenovirus (ADV), norovirus or both had been previously detected by clinical diagnostic qPCRs (Diagnosis D), while in 5 samples no viral GI pathogens were found (No diagnosis ND). In all D samples the presence of the initially found virus could be confirmed upon ViroCap analysis. ADV was most commonly found and Ct values grossly correlated with the number of sequence specific reads upon ViroCap GD and DA analysis. In addition, ViroCap led to the detection of multiple, possibly clinically relevant viral pathogens in D samples, including human herpesvirus-6B (HHV6B) (n=1), BK polyomavirus (BKV) (n=2), ADV (n=1) and human rhinovirus (HRV) (n=1). Presence of BKV and HRV was confirmed by qPCR. Furthermore, in 4/5 ND samples viral pathogens were detected. These included human herpes Virus 7 (HHV7) (n=1), BKV (n=1), HRV (n=2) and Astrovirus (AV) (n=1). HRV presence was confirmed by qPCR, HHV7 was not tested. BKV could not be confirmed, but other clinical samples from the same patient taken closely before/after the specific stool sample were BKV positive. Further analysis of the AV sequences revealed that the routine PCR failed to detect this virus due to extensive sequence mismatches in the primer/probe binding regions. This AV clade was classified as an AV VA3 (JX857868.1). In summary, application of viral target enrichment strategies with limited pathogen detection bias, such as ViroCap, increase the sensitivity of NGS for virus detection and can lead to discovery of novel variants. As such, it might be a useful screening tool to study associations of viral pathogens with GI-symptoms and GVHD. [ABSTRACT FROM AUTHOR]
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- 2020
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8. Microbial Dysbiosis in Common Variable Immune Deficiencies: Evidence, Causes, and Consequences.
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Berbers, Roos-Marijn, Nierkens, Stefan, van Laar, Jacob M., Bogaert, Debby, and Leavis, Helen L.
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IMMUNODEFICIENCY , *IMMUNOLOGIC diseases , *MICROBIOLOGY , *IMMUNE system , *RETINOIC acid syndrome - Abstract
Common variable immunodeficiency (CVID) is an immune disorder that not only causes increased susceptibility to infection, but also to inflammatory complications such as autoimmunity, lymphoid proliferation, malignancy, and granulomatous disease. Recent findings implicate the microbiome as a driver of this systemic immune dysregulation. Here, we critically review the current evidence for a role of the microbiome in the pathogenesis of CVID immune dysregulation, and describe the possible immunologic mechanisms behind causes and consequences of microbial dysbiosis in CVID. We integrate this evidence into a model describing a role for the gut microbiota in the maintenance of inflammation and immune dysregulation in CVID, and suggest research strategies to contribute to the development of new diagnostic tools and therapeutic targets. [ABSTRACT FROM AUTHOR]
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- 2017
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9. Air pollution from livestock farms and the oropharyngeal microbiome of COPD patients and controls.
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van Kersen, Warner, Bossers, Alex, de Steenhuijsen Piters, Wouter A.A., de Rooij, Myrna M.T., Bonten, Marc, Fluit, Ad C., Heederik, Dick, Paganelli, Fernanda L., Rogers, Malbert, Viveen, Marco, Bogaert, Debby, Leavis, Helen L., and Smit, Lidwien A.M.
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AIR pollution , *LIVESTOCK farms , *CHRONIC obstructive pulmonary disease , *AIR pollutants - Abstract
[Display omitted] Air pollution from livestock farms is known to affect respiratory health of patients with chronic obstructive pulmonary disease (COPD). The mechanisms behind this relationship, however, remain poorly understood. We hypothesise that air pollutants could influence respiratory health through modulation of the airway microbiome. Therefore, we studied associations between air pollution exposure and the oropharyngeal microbiota (OPM) composition of COPD patients and controls in a livestock-dense area. Oropharyngeal swabs were collected from 99 community-based (mostly mild) COPD cases and 184 controls (baseline), and after 6 and 12 weeks. Participants were non-smokers or former smokers. Annual average livestock-related outdoor air pollution at the home address was predicted using dispersion modelling. OPM composition was analysed using 16S rRNA-based sequencing in all baseline samples and 6-week and 12-week repeated samples of 20 randomly selected subjects (n = 323 samples). A random selection of negative control swabs, taken every sampling day, were also included in the downstream analysis. Both farm-emitted endotoxin and PM 10 levels were associated with increased OPM richness in COPD patients (p < 0.05) but not in controls. COPD case-control status was not associated with community structure, while correcting for known confounders (multivariate PERMANOVA p > 0.05). However, members of the genus Streptococcus were more abundant in COPD patients (Benjamini-Hochberg adjusted p < 0.01). Moderate correlation was found between ordinations of 20 subjects analysed at 0, 6, and 12 weeks (Procrustes r = 0.52 to 0.66; p < 0.05; Principal coordinate analysis of Bray-Curtis dissimilarity), indicating that the OPM is relatively stable over a 12 week period and that a single sample sufficiently represents the OPM. Air pollution from livestock farms is associated with OPM richness of COPD patients, suggesting that the OPM of COPD patients is susceptible to alterations induced by exposure to air pollutants. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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