Henk-Jan van den Ham

ENPICOM

Systems vaccinology has seldomly been used in therapeutic HIV-1 vaccine research. Our aim was to identify early gene ‘signatures’ that predicted virus load control after analytical therapy interruption (ATI) in participants of a dendritic cell-based HIV-1 vaccine trial (DCV2). mRNA and miRNA were extracted from frozen post-vaccination PBMC samples;...

Primary varicella-zoster virus (VZV) infection in adults is often complicated by severe pneumonia, which is difficult to treat and associated with high morbidity and mortality. Here, the simian varicella virus (SVV) nonhuman primate (NHP) model was used to investigate the pathogenesis of varicella pneumonia. SVV infection resulted in transient feve...

Herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) are two closely related human alphaherpesviruses that persistently infect most adults worldwide and cause a variety of clinically important diseases. Herpesviruses are extremely well adapted to their hosts and interact broadly with cellular proteins to regulate virus replication and sp...

Background In recent years, researchers have had an increased focus on multiplex microarray assays, in which antibodies are measured against multiple related antigens, for use in seroepidemiological studies to infer past transmission. Methods We assess the performance of a flavivirus microarray assay for determining past dengue virus (DENV) infect...

Helper T cell differentiation is a key process in the regulation of adaptive immune responses. Here, we profile mouse Th1 and Th2 cells using high‐throughput proteomics to increase our understanding of the molecular biology of Th differentiation to support the design of prophylactic and therapeutic intervention strategies for (infectious) diseases....

Measles causes a transient immune suppression, leading to increased susceptibility to opportunistic infections. In experimentally infected non-human primates (NHPs) measles virus (MV) infects and depletes pre-existing memory lymphocytes, causing immune amnesia. A measles outbreak in the Dutch Orthodox Protestant community provided a unique opportun...

Objective: The efficacy of therapeutic vaccines against HIV-1 infection has been modest. New inerts to redirect responses to vulnerable sites are urgently needed to improve these results. Design: We performed the first-in-human clinical trial with naked mRNA (iHIVARNA) combining a DC activation strategy (TriMix:CD40L+CD70+caTLR4 RNA) with a nove...

Nuclear receptors (NRs) are ligand-inducible transcription factors that play critical roles in metazoan development, reproduction and physiology, and, as a consequence, are implicated in a broad-range of pathologies. The transcriptional activity of NRs critically depends on their interaction(s) with transcriptional coregulator proteins, including c...

Rabies is an important neglected disease, characterized by invariably fatal encephalitis. Several studies focus on understanding the pathogenic mechanisms of the prototype lyssavirus rabies virus (RABV) infection, and little is known about the pathogenesis of rabies caused by other lyssaviruses. We sought to characterize the host response to Duvenh...

Objectives To characterize the host response to dendritic cell-based immunotherapy and subsequent combined antiretroviral therapy (cART) interruption in HIV-1-infected individuals at the plasma protein level. Design An autologous dendritic cell (DC) therapeutic vaccine was administered to HIV-infected individuals, stable on cART. The effect of vac...

Association of TBG expression with time off therapy. Vertical grey lines connect samples from a single patient. The dotted diagonal lines represent regression lines that represent time off treatment vs TBG expression at specific trial stages. (EPS)

Details of Cox proportional hazards model. List of analytes that have borderline significance and are considered to be worth further study. (XLSX)

Group-wise expression of all analytes. Boxplots of analyte expression per group for every analyte that passed quality control. (PDF)

Patients have strong individual cytokine profiles that can be partially corrected. Principle component analysis of samples from HIV-infected individuals only before (A) and after (B) removal of the patient effect. (EPS)

Heatmap of analytes from all samples. Samples from the same patient tend to cluster together. (EPS)

Analyse measurements for all samples. This table contains the primary analyte data that this study is based on. (XLSX)

Analyte quality control. Number and proportion of missing values in the analytes that passed quality control. (XLSX)

Distribution of cytokine expressions. A—38 cytokines show little or no variance and have been removed from the dataset. B—Distribution of cytokine levels in a sample. No samples need to be removed as a result of insufficient quality. (EPS)

Background: The 1918 Spanish H1N1 influenza pandemic was the most severe recorded influenza pandemic with an estimated 20-50 million deaths worldwide. Even though it is known that influenza viruses can cause extra-respiratory tract complications-which are often severe or even fatal- the potential contribution of extra-respiratory tissues to the pa...

West Nile virus (WNV) and chikungunya virus (CHIKV) are arboviruses that are constantly (re-)emerging and expanding their territory. Both viruses often cause a mild form of disease, but severe forms of the disease can consist of neurological symptoms, most often observed in the elderly and young children, respectively, for which the mechanisms are...

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature CD5⁺ B cells in blood. Spontaneous apoptosis of CLL cells in vitro has hampered in-depth investigation of CLL pathogenesis. Here we describe the generation of three monoclonal mouse cell lines, EMC2, EMC4 and EMC6, from the IgH.TEμ CLL mouse model based on sporadic ex...

Purpose: To investigate which cytokines and chemokines are involved in the immunopathogenesis of acute retinal necrosis (ARN), and whether cytokine profiles are associated with clinical manifestations, such as visual outcome. Methods: Serum and aqueous humor (AH) samples of 19 patients with ARN were analyzed by multiplex immunoassay. Infectious...

With the advent of high-throughput proteomics, the type and amount of data pose a significant challenge to statistical approaches used to validate current quantitative analysis. Whereas many studies focus on the analysis at the protein level, the analysis of peptide-level data provides insight into changes at the sub-protein level, including splice...

Respiratory syncytial virus (RSV) causes infections that range from common cold to severe lower respiratory tract infection requiring high-level medical care. Prediction of the course of disease in individual patients remains challenging at the first visit to the pediatric wards and RSV infections may rapidly progress to severe disease. In this stu...

Seropositivity to avian influenza (AI) via low-level antibody titers has been reported in the general population and poultry-exposed individuals, raising the question whether these findings reflect true infection with AI or cross-reactivity. Here we investigated serological profiles against human and avian influenza viruses in the general populatio...

Background: Cellular development is directed by multiple factors, including extra-cellular stimuli that are communicated from the cell membrane to the interior by signal transduction cascades. Such signalling cascades can be quantified by phospho-proteomics (LC-MS/MS) in, for instance, differentiation of helper T cells into different immune effecto...

Dengue virus (DENV) infection causes viral haemorrhagic fever that is characterized by extensive activation of the immune system. The aim of this study is to investigate the kinetics of the transcriptome signature changes during the course of disease and the association of genes in these signatures with clinical parameters. Sequential whole blood s...

Unlabelled: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants. Despite over 50 years of research, to date no safe and efficacious RSV vaccine has been licensed. Many experimental vaccination strategies failed to induce balanced T-helper (Th) responses and were associated with adverse effects su...

Background During a dengue outbreak on the Caribbean island Aruba, highly elevated levels of ferritin were detected in dengue virus infected patients. Ferritin is an acute-phase reactant and hyperferritinaemia is a hallmark of diseases caused by extensive immune activation, such as haemophagocytic lymphohistiocytosis. The aim of this study was to i...

Current avian influenza surveillance in poultry primarily targets subtypes of interest for the veterinary sector (H5, H7). However, as virological and serological evidence suggest, surveillance of additional subtypes is important for public health as well as for the poultry industry. Therefore, we developed a protein microarray enabling simultaneou...

Patients suffering from advanced melanoma have a very poor prognosis. Despite recent advances in the understanding of oncogenic mechanisms and therapeutic interventions, the median survival of patients with metastatic disease is less than 12 months. Immunotherapy of melanoma has been intensely investigated and holds great promises. Tyrosinase-relat...

Background: Endothelial cell dysfunction is believed to play an important role in the pathogenesis of plasma leakage in patients with acute dengue virus (DENV) infection. Several factors, produced by activated endothelial cells, have been associated with plasma leakage or severe disease in patients with infectious diseases. Objectives: The aim o...

This technical note describes fq _delta, a python module and shell script that enables the storage of processed versions of fastq files generated by DNA and RNA sequencing technologies. By using Myer's diff algorithm to perform per-character comparisons between the original and processed fastq files, we generate delta files that describe the change...

Helper T cell differentiation (Th) is a key event in the development of the adaptive immune response. By the production of a range of cytokines, Th cells determine the type of immune response that is raised against an invading pathogen. Th cells can adopt many different phenotypes and Th phenotype decision-making is crucial in mounting effective ho...

Cytokine levels in dengue virus infected patients classified according to the occurrence of hemorrhage. A: IL-6: Levels are significantly elevated in patients with severe bleeding compared to patients with no hemorrhage (P = 0,001) (KW P = 0,007, KW dengue groups P = 0,003). B: IL-8: Levels in patients with severe bleeding are significantly elevate...

STROBE Checklist. STROBE checklist for this study. (DOC)

Cytokine levels in dengue virus infected patients are significantly different compared to healthy controls. A: IFN-α: Levels in DENV infected patients are significantly elevated compared to HC (WS− vs HC P = 0,001, WS+ vs HC P = 0,003 and severe vs HC P = 0,001, KW P = 0,005, KW dengue groups P = 0,93). B: IL-15: Levels in DENV infected patients ar...

Levels of cytokines during the course of disease. A: IFN-α: Levels at day 1–3 were significantly increased compared to day 4–7 (P = 0,002) and day>7 (P = 0,003) (KW P = 0,001). B: MCP-1: Levels at day 1–3 were significantly increased compared to day 4–7 (P<0,0001) and day>7 (P<0,0001) (KW P<0,0001). C: MIG: Levels at day 1–3 were significantly incr...

Hypothesis: Childhood obesity is accompanied by low-grade systemic inflammation, which contributes to the development of insulin resistance and cardiovascular complications later in life. As vitamin D exhibits profound immunomodulatory functions and vitamin D deficiency is highly prevalent in childhood obesity, we hypothesized that vitamin D defic...

Severe dengue virus (DENV) disease is associated with extensive immune activation, characterized by a cytokine storm. Previously, elevated lipopolysaccharide (LPS) levels in dengue were found to correlate with clinical disease severity. In the present cross-sectional study we identified markers of microbial translocation and immune activation, whic...

Th cells can adopt a number of different phenotypes. We performed microarray-assisted mRNA profiling on antigen-stimulated, TCR transgenic murine splenocytes that were cultured in the presence of cytokines. Transcriptome snapshots of Th cells differentiating into Th1 and Th2 phenotypes were obtained at various time points. Principal component analy...

In adults, circulating inflammatory mediators and activated CD14(++) monocytes link obesity to its metabolic and cardiovascular complications. However, it is largely unknown whether these inflammatory changes already occur in childhood obesity. To survey inflammatory changes during the early stages of obesity, we performed a comprehensive analysis...

Following activation by antigen, helper T cells differentiate into one of many effector phenotypes. Formulating mechanistic mathematical models combining regulatory networks at the transcriptional, translational and epigenetic level, we study how individual helper T cells may adopt their different phenotypes. For each cytokine phenotype, for exampl...

The T helper paradigm is currently being revised from the Th1-Th2 dichotomy to a multi-state paradigm involving a number of different cell phenotypes. Transcriptional profiling using microarrays has been used to study the development of these phenotypes. There is however no clear consensus on how to approach the analysis of this data, especially in...

Bootstrapping to account for variability. (0.02 MB DOC)

Results of the linear regression analysis of the weight loss and all factors in gaining and moderately wasting mice. (0.04 MB DOC)

Removing severely wasting mice from the analysis. (0.02 MB DOC)

Selecting a minimal model. Akaike and Bayesian Information Criterion. (0.02 MB DOC)

Multiple regression analysis and F-tests. (0.02 MB DOC)

Correlation between disease progression (as determined by the weight loss at day 24 post-infection) and Mtb load for female mice. Dashes blue line, the prediction of the linear regression between weight loss and Mtb load when all mice are included in the analysis; solid black line, the same when severely wasting mice (shown by blue crosses) are exc...

Background: Infection with Mycobacterium tuberculosis (Mtb) results in different clinical outcomes ranging from asymptomatic containment to rapidly progressing tuberculosis (TB). The mechanisms controlling TB progression in immunologically-competent hosts remain unclear. Methodology/principal findings: To address these mechanisms, we analyzed TB...

Helper T cells play an important role in determining the outcome of an immune response. Helper T cells of distinct phenotypes induce different immune responses by producing distinct cytokines. The phenotype of a helper T cell and the production of the corresponding cytokine(s) is determined by so-called `master transcription factors', and is subseq...

With the introduction of high-throughput biomarker measurements, traditional analysis of these markers is increasingly difficult. Using samples from a diverse group of patients, we tested the applicability of cluster analysis to these data. Using this method, we aim to visualize some of the patterns specific to certain disease groups. In particular...