Sven Olek

Sven Olek
Epiontis GmbH · Research and Development

PhD

About

144
Publications
10,944
Reads
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6,894
Citations
Citations since 2016
45 Research Items
3775 Citations
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
Introduction
Skills and Expertise
Education
January 1993 - January 1996
Imperial College London
Field of study
  • biochemistry

Publications

Publications (144)
Article
Although ample evidence indicates that immune cell homeostasis is an important prognostic outcome determinant in patients with cancer, few studies have examined whether it also determines cancer risk among initially healthy individuals. We performed a case–cohort study including incident cases of breast (n = 207), colorectal (n = 111), lung (n = 70...
Article
Immune cell subtype population frequencies can have a large effect on the efficacy of T cell therapies. Current methods, like flow cytometry, have specific sample requirements, high sample input, are low throughput, and are difficult to standardize, all of which are detrimental to characterization of cell therapy products during their development a...
Article
Background: Immune-dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome is a lethal disease caused by mutations in a transcription factor critical for the function of thymus-derived (t) regulatory T cells (Tregs), i.e., Forkhead-box-P3 (FOXP3), resulting in impaired Treg function and autoimmunity. At present, hematopoietic stem...
Article
Full-text available
Objective: To investigate whether epigenetic cell counting represents a novel method to quantify immune cells in salivary glands of patients with different forms of Sjögren's and sicca syndrome and to capture immunopathology and potentially aid in diagnosis. Methods: DNA from frozen salivary gland tissue sections of sicca patients was used for b...
Article
Full-text available
Abstract Objective The diagnosis of RA patients remains a challenge, especially in ACPA-negative disease. Novel T-cell subsets, particularly Th17 may be useful, although data on Th17 frequency using flow cytometry in RA are conflicting. We investigated whether a novel epigenetic qPCR assay for the quantification of Th17 could differentiate patien...
Article
Full-text available
Authors are to be congratulated for an important paper on the rate of settlement approach originated by Tewatia (1998a) that is a promising interpretation tool to find c v and δ eop along with other consolidation parameters. Conclusions of authors by experiments on different clays are in agreement with earlier conclusions drawn by Tewatia (1998a, b...
Article
Full-text available
Adoptive transfer of regulatory T cells (FOXP3+ Tregs) has been developed as a potential curative immune therapy to prevent and treat autoimmune and graft-versus-host diseases (GVHD). A major limitation that has hindered the use of Treg immunotherapy in humans is the difficulty of consistently isolating and obtaining highly purified Tregs after ex...
Article
Immune cell profiles provide valuable diagnostic information for hematologic and immunologic diseases. Although it is the most widely applied analytical approach, flow cytometry is limited to liquid blood. Moreover, either analysis must be performed with fresh samples or cell integrity needs to be guaranteed during storage and transport. We develop...
Article
Full-text available
Immunosenescence is a hallmark of the aging immune system and is considered the main cause of a reduced vaccine efficacy in the elderly. Although γδ T cells can become activated by recombinant influenza hemagglutinin, their age-related immunocompetence during a virus-induced immune response has so far not been investigated. In this study we evaluat...
Data
Kinetics of absolute counts and frequencies. Vaccination-dependent kinetics of absolute counts and frequencies of the γδ T cell subsets in Figs 2 and 3A) Absolute counts of γδTCR+Ki67+. B) Absolute counts of γδTCR+CD38+Ki67+. C) Frequency of total CD38+ among γδTCR+ T cells. D) Frequency of CD38+Ki67– among γδTCR+ T cells. The box represents the 25...
Data
Association of frequencies to day 21 HAI titers of B/Brisbane/60/2008. Association of day 21 HAI titers of B/Brisbane/60/2008-like virus to A) the frequency of total Ki67+ among γδTCR+ and B) the frequency of CD38+Ki67+ among γδTCR+ at day 3 and 7 for the young and the elderly. Correlation by the Spearman rank method. Each point indicates a donor....
Data
Association of proportionality constant and day 21 HAI titers. Association of day 0–3 proportionality constant of the frequency of total Ki67+ among γδTCR+ T cells and frequency of CD38+Ki67+ among γδTCR+ T cells for young and elderly (Fig 2B and 2E) to the day 21 HAI titers of the A) and D) A/California/7/2009 (H1N1), B) and E) A/Perth/16/2009 (H3...
Data
Characterization of activation of γδ T cells. A) The gating strategy applied to identify activated γδTCR+ T cells. Shown is a representative donor. B and C) Activation status of γδTCR+ T cells at baseline in the young donors in Fig 1B separated into low (< 10%) and high (> = 10%) baseline frequency of γδTCR+ T cells. D) Representative Ki67 stain at...
Data
CMV status and kinetics of absolute counts and frequencies. Vaccination-dependent kinetics of absolute counts and frequencies of the γδ T cell subsets in Figs 2 and 3, with age groups subdivided into CMV negative and CMV positive. A) Frequency of total Ki67+ among γδTCR+ T cells. B) Frequency of CD38+Ki67+ among γδTCR+ T cells. C) Absolute counts o...
Article
Objectives: The aim of the present study was to assess in a large cohort of primary epithelial ovarian cancer patients the incidence and the clinical effect of BRCA1 genetic and epigenetic silencing mechanisms. Methods: A total of 188 primary epithelial ovarian cancer patients, treated between 2000 and 2011 at the Charité University Hospital of...
Conference Paper
Background Histological analysis of salivary glands for decades has been a valuable tool in the characterization of patients with primary Sjögren's syndrome (pSS) and non-Sjögren's sicca (nSS) patients. Importantly, it has helped in understanding the immunopathology of sicca patients. Nonetheless, standardization of histological assessments, e.g. t...
Article
We examined tolerance mechanisms in patients receiving HLA-mismatched combined kidney and bone marrow transplantation (CKBMT) that led to transient chimerism under a previously-published non-myeloablative conditioning regimen (Immune Tolerance Network study ITN036). Polychromatic flow cytometry (FCM) and high throughput sequencing of TCRβ hypervari...
Article
Full-text available
Exposure to high concentrations of the phthalate metabolite mono-isobutyl phthalate (MiBP) in the prenatal period is a risk factor for atopic dermatitis in early childhood, presumably by inhibiting the development of regulatory T cells.
Article
Recent clinical trials have indicated the high potential of regulatory T cells (Tregs) in the prevention of acute and chronic graft-versus-host disease (GvHD) after hematopoietic stem cell transplantation, but immune interventions require large numbers of Tregs. With respect to their limited natural occurrence, development and optimization of proto...
Article
E- and P-selectin ligands (E- and P-ligs) guide effector memory T cells into skin and inflamed regions, mediate the inflammatory recruitment of leukocytes, and contribute to the localization of hematopoietic precursor cells. A better understanding of their molecular regulation is therefore of significant interest with regard to therapeutic approach...
Data
Supplementary material. 3 Tables, 2 Figures.
Article
Full-text available
Background: Experimental and clinical evidence indicate that inflammatory processes in atherogenesis and the development of cardiovascular complications are promoted by a loss of regulatory T cell (Treg)-mediated immunological tolerance to plaque antigens. Yet, the association between alterations of systemic Treg frequency and cardiovascular disea...
Article
Germline mutations in BRCA1 gene have been reported in up to 20 % of epithelial ovarian cancer (EOC) patients. Distinct clinical characteristics have been attributed to this special EOC population. We hypothesized that mutations in different BRCA1 gene exons may differently affect the clinical course of the disease. The aim of this study was to ana...
Article
Full-text available
Understanding the immune response after vaccination against new influenza strains is highly important in case of an imminent influenza pandemic and for optimization of seasonal vaccination strategies in high risk population groups, especially the elderly. Models predicting the best sero-conversion response among the three strains in the seasonal va...
Data
Logistic regression models with monocytes (CD14+), natural killer (CD56+ NK) cells, dendritic cells (pDCs), plasmablasts and influenza specific activated (CD4+CD40L+) cells in the pilot study. Plasmablasts counts are significantly (p = 0.03) different between H1N1 protected and non-protected vaccinees, while the other sub-populations in this figure...
Data
Prediction of non-protection to A(H1N1)pdm09 strain as function of the combination of age, NSSN, CD4+ T cells and B cells in the pilot study. Using multi-variate logistic regression shows that the combination of age, number of sero-negative strains (NSSN), CD4+ T-cell counts and B-cell counts at baseline give a predictive model with high significan...
Data
Gating strategy for identification of B-cell subsets. The figure is showing the gating strategy for the identification of CD19+ B-cells and its subsets. M = Memory, N = Naive. (TIF)
Data
Gating strategy for identification of regulatory T-cell populations. The figure is showing the gating strategy for the identification of regulatory T-cell populations. nTreg = natural regulatory T-cells, N = Naïve, M = Memory. (TIF)
Data
Gating strategy for identification of Plasmablasts. The figure is showing the gating strategy for the identification of Plasmablasts. (TIF)
Data
Hierarchical network representation of immune cell-subset counts at baseline with respect to the Perth strain protection in the pilot study. Overall, 36 immune cell subsets at baseline were analyzed and compared in Perth sero-negative donors with or without sero-protection for the Perth strain after vaccination using the Wilcoxon test. P-values bel...
Data
Baseline immune cell counts as a function of age in the pilot study. The counts of CD8+ T cells and Monocytes are significantly different between young and old donors (two-sided Wilcoxon test, p<0.05). (TIF)
Data
Baseline immune cell counts as a function of NSSN in the pilot study. No significant differences related to the number of sero-negative strains were observed in A(H1N1)pdm09 sero-negative donors. (TIF)
Data
Pilot study data. The table includes all data which were used to do the analysis presented in the paper for the pilot study. The first three columns contain the ids, the age (in years) and the gender (F-female, M-male) of the donors. The following six columns show the HAI titer for each virus strain prior to (day0) and after (day21) vaccination. Pl...
Data
Logistic regression models with age only, CD4+ T cells, Lymphocytes and Leukocytes in the pilot study. Age, CD4 T-cell and lymphocyte counts are significantly (p = 0.01, p = 0.04 and p = 0.05, respectively) different between H1N1 protected and non-protected vaccinees, while leukocytes show no significant association with protection on their own. Le...
Data
Gating strategy for identification of Dendritic cells. The figure is showing the gating strategy for the identification of Dendritic cell populations. C = Classical Monocytes, NC—Non-classical Monocytes, T = Transitional Monocytes, pDC = plasmacytoide dendritic cells, mDC = myeloide dendritic cells. (TIF)
Data
Gating strategy for identification of Natural Killer cells (NK). The figure is showing the gating strategy for the identification of Natural Killer cells. (TIF)
Data
Gating strategy for identification of influenza specific CD4+CD40L+ cells. The figure is showing the gating strategy for the identification of influenza specific CD4+CD40L+ cells. (TIF)
Data
Hierarchical network representation of immune cell-subset counts at baseline with respect to the Brisbane strain protection in the pilot study. Overall, 36 immune cell subsets at baseline were analyzed and compared in Brisbane sero-negative donors with or without sero-protection for the Brisbane strain after vaccination using the Wilcoxon test. P-v...
Data
Logistic regression models with CD4+ T cells, naive CD4+ T cells, naive CD4+CD31+ recent thymic emigrants T cells (RTE) and naive CD4+CD31- non-RTE T cells in the pilot study. Counts of CD4 total T-cells, CD4 Naive T-cells, CD4 Naïve RTE T-cells and CD4 Naïve non-RTE T-cells are all significantly (p = 0.02, p = 0.002, p = 0.009 and p = 0.005, respe...
Data
Gating strategy for identification of T-cell subsets. The figure is showing the gating strategy for the identification of CD3+ T-cells and its subsets CD4+ and CD8+ T-cells. EM = Effector Memory, CM = Central Memory, Eff = Effector, N = Naïve, RTE = Recent Thymic Emigrants. (TIF)
Data
Gating strategy for identification of proliferating CD4+ and CD8+ cells. The figure is showing the gating strategy for the identification of CD4+Ki67+ and CD8+Ki67+ cells. (TIF)
Data
Validation study data. The table includes all data which were used to do the analysis presented in the paper for the validation study. The first three columns contain the ids, the age (in years) and the gender (F-female, M-male) of the donors. The following six columns show the HAI titer for each virus strain prior to (day0) and after (day21) vacci...
Article
Full-text available
Background A considerable interest has risen about the interplay between immune suppression and polarisation particularly with Th17 cells. Although Th2 polarisation seems intact in rheumatoid arthritis (RA), Th1 has long been known to be perturbed with lack of appropriate epigenetic commitment. Defective polarisation could be a mechanism by which T...
Article
Full-text available
High doses of zinc oxide are commonly used in weaned pig diets to improve performance and health. Recent reports show that this may also lead to an imbalanced zinc homeostasis in the animal. For a better understanding of the regulatory mechanisms of different zinc intakes, we performed a feeding experiment to assess potential epigenetic regulation...
Article
Full-text available
Laboratory-based, mechanistic, and prognosis studies suggest that a shift from antitumor immunity towards tumor-immune tolerance plays a major role in carcinogenesis. However, prospective epidemiological studies on the consequences of differing immune tolerance levels prior to clinical manifestation are missing. A case-cohort study embedded in EPIC...
Article
Full-text available
Background: The FOXP3 gene is the master regulator for T regulatory cells and is under tight DNA methylation control at the Treg specific demethylated region (TSDR) in its first intron. This said, methylation of its promoter region, the significance of which is unknown, has also been associated with various immune-related disease states such as as...
Article
Autologous hematopoietic stem cell transplantation (HSCT) is increasingly considered for patients with severe autoimmune diseases whose prognosis is poor with standard treatments. Regulatory T cells (Tregs) are thought to be important for disease remission after HSCT. However, eliciting the role of donor and host Tregs in autologous HSCT is not pos...
Article
Full-text available
Immunosenescence results from a continuous deterioration of immune responses resulting in a decreased response to vaccines. A well-described age-related alteration of the immune system is the decrease of de novo generation of T and B cells. In addition, the accumulation of memory cells and loss of diversity in antigen specificities resulting from a...
Article
Immunosenescence is a hallmark of the aging immune system, leading to increased susceptibility to infections in the aged population and decreased ability to eradicate infectious pathogens. These effects, in turn, result in an increased burden on the healthcare system due to elevated frequency and duration of hospital visits. Growing evidence sugges...
Article
Regulatory T cells (Tregs) are known to play critical roles in homeostasis and immune responses in the skin. Whether Treg frequencies are altered in atopic dermatitis (AD) patients has been addressed by several studies, leading to conflicting results. The detection of Tregs by FOXP3-expression may lead to false positive results since activated T ce...
Article
Full-text available
Epigenetic research leads to complex data structures. Since parametric model assumptions for the distribution of epigenetic data are hard to verify we introduce in the present work a nonparametric statistical framework for two-group comparisons. Furthermore, epigenetic analyses are often performed at various genetic loci simultaneously. Hence, in o...
Article
Full-text available
Statins have been shown to modulate the number and the suppressive function of CD4+FOXP3+ T cells (Treg) in inflammatory conditions. However, it is not well established whether statin could also affect Treg in absence of inflammation. To address this question, eighteen normocholesterolemic male subjects were treated with lovastatin or atorvastatin...
Article
Full-text available
Regulatory T cells (Tregs) are potentially prognostic indicators in patients with glioblastoma. If differences in frequency of Tregs in tumor or blood account for substantial variation in patient survival, then reliably measuring Tregs may enhance treatment selection and improve outcomes. We measured Tregs and CD3+ T cells in tumors and blood from...
Article
Adoptive transfer of regulatory T (Treg) cells could be an alternative to chronic immunosuppression for prevention of allogeneic graft rejection. While polyspecific Treg cells can prevent immune responses under lymphopenic conditions, antigen-specific Treg cells are needed to treat autoimmunity and graft rejection. Yet, reliable markers for antigen...
Article
Full-text available
The imbalance between Th17 and Treg cells has been studied in various diseases including allergic asthma but their roles have not been fully understood in the development of the late phase asthmatic response. To determine changes in Th17 and Treg cell numbers between isolated early responders (ERs) and dual responders (DRs) undergoing allergen inha...
Article
Full-text available
Hematopoietic Stem Cell Transplantation (HSCT) from HLA haploidentical family donors is a promising therapeutic option for high-risk hematologic malignancies. Here we explored in 121 patients, mostly with advanced stage diseases, a sirolimus-based, calcineurin-inhibitor-free prophylaxis of Graft-versus-Host Disease (GvHD) to allow the infusion of u...
Article
Background: Mutations in BRCA1/2 genes are involved in the pathogenesis of breast and ovarian cancer. Inactivation of these genes can also be mediated by hypermethylation of CpGs in the promoter regions. Aim of this study was to analyse the clinical impact of BRCA1 promoter gene methylation status in a homogenous cohort of high-grade serous ovaria...
Article
Background & aims: Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease usually requiring life-long immunosuppression. The mechanisms for disease initiation and chronicity are largely unknown. A contribution of deficient regulatory T cells (Tregs) in the blood was controversially discussed recently. So far investigations in the target...
Article
Full-text available
Background Atopic allergic asthmatic individuals experience acute bronchoconstriction (early response) upon allergen exposure. Several hours after the initial exposure, some individuals exhibit a chronic late phase (dual responders, DRs) whereas others do not (early responders, ERs). The purpose of this study is to determine changes in Th17 and reg...
Article
Recently, genome wide association studies in primary sclerosing cholangitis (PSC) revealed associations with gene polymorphisms that potentially could affect the function of regulatory T cells (Treg). The aim of this study was to investigate Treg in patients with PSC and to associate their numbers with relevant gene polymorphisms. Treg frequency in...
Article
The transfer of alloreactive Treg (aTreg) cells into transplant recipients represents an attractive treatment option to improve long-term graft acceptance. We recently described a protocol for the generation of aTreg cells in mice using a non-depleting anti-CD4 antibody (aCD4). Here we investigated whether adding TGF-β and retinoic acid (RA) or rap...