Claus Bachert

Karolinska Institutet, Solna, Stockholm, Sweden

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Publications (486)2014.73 Total impact

  • PLoS ONE 06/2015; 10(6):e0128564. DOI:10.1371/journal.pone.0128564 · 3.53 Impact Factor
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    ABSTRACT: Background The most prevalent phenotype of asthma is characterized by eosinophil-dominated inflammation that is driven by a type 2 helper T cell (Th2). Therapeutic targeting of GATA3, an important transcription factor of the Th2 pathway, may be beneficial. We evaluated the safety and efficacy of SB010, a novel DNA enzyme (DNAzyme) that is able to cleave and inactivate GATA3 messenger RNA (mRNA). Methods We conducted a randomized, double-blind, placebo-controlled, multicenter clinical trial of SB010 involving patients who had allergic asthma with sputum eosinophilia and who also had biphasic early and late asthmatic responses after laboratory-based allergen provocation. A total of 40 patients could be evaluated; 21 were assigned to receive 10 mg of SB010, and 19 were assigned to receive placebo, with each study drug administered by means of inhalation once daily for 28 days. An allergen challenge was performed before and after the 28-day period. The primary end point was the late asthmatic response as quantified by the change in the area under the curve (AUC) for forced expiratory volume in 1 second (FEV1). Results After 28 days, SB010 attenuated the mean late asthmatic response by 34%, as compared with the baseline response, according to the AUC for FEV1, whereas placebo was associated with a 1% increase in the AUC for FEV1 (P=0.02). The early asthmatic response with SB010 was attenuated by 11% as measured by the AUC for FEV1, whereas the early response with placebo was increased by 10% (P=0.03). Inhibition of the late asthmatic response by SB010 was associated with attenuation of allergen-induced sputum eosinophilia and with lower levels of tryptase in sputum and lower plasma levels of interleukin-5. Allergen-induced levels of fractional exhaled nitric oxide and airway hyperresponsiveness to methacholine were not affected by either SB010 or placebo. Conclusions Treatment with SB010 significantly attenuated both late and early asthmatic responses after allergen provocation in patients with allergic asthma. Biomarker analysis showed an attenuation of Th2-regulated inflammatory responses. (Funded by Sterna Biologicals and the German Federal Ministry of Education and Research; number, NCT01743768 .).
    New England Journal of Medicine 05/2015; DOI:10.1056/NEJMoa1411776 · 54.42 Impact Factor
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    ABSTRACT: In adults, subjects sensitised to Staphylococcus aureus enterotoxins (SE) seem to have an increased risk of asthma, whereas this association is less clear in childhood and adolescence. The primary aim of the present analysis was to examine the association between sensitisation to SE and asthma at the age of 20 years. The German Multicentre Allergy Study recruited 1314 healthy new-borns in 1990. We analysed data from 61 asthmatics (based on at least two criteria: physician diagnosed asthma ever, wheezing in the last 12 months, asthma medication in the last 12 months) and 122 healthy study participants at age 20. In serum, specific Immunoglobulin E (IgE) to SE and common aero-allergens were measured. The association between asthma at age 20 and sensitisation to SE was estimated by logistic regression models considering allergic, socio-demographic and lifestyle factors as potential confounders. Fifty-five percent of the included participants were female. At age 20, subjects sensitised to SE were more likely to have asthma than not-sensitised subjects: raw odds ratio (OR), [95%-confidence interval (95%CI)] 2.5 [1.3-4.7]; adjusted OR [95%-CI] 1.6 [0.8-3.4]. Asthmatics at age 20 were more often sensitized to SE compared to controls. Our study may indicate a moderate relationship between SE-sensitisation and asthma; however, this association attenuated after adjusting for potential confounders and was no longer statistically significant. Longitudinal investigations with SE-IgE measurements at different time points in larger samples are needed to explore the temporal manner of this relationship. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Pediatric Allergy and Immunology 05/2015; DOI:10.1111/pai.12396 · 3.86 Impact Factor
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    ABSTRACT: Allergic diseases (asthma, rhinitis and atopic dermatitis) are complex. They are associated with allergen-specific IgE and non-allergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono or polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE-mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re-occurrence of foetal Type 2 signalling. Asthma, rhinitis and atopic dermatitis are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This paper proposes a new classification of IgE-mediated allergic diseases that allows the definition of novel phenotypes in order to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis, and (iii) propose novel strategies of treatment and prevention. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Allergy 04/2015; DOI:10.1111/all.12637 · 6.00 Impact Factor
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    PLoS ONE 04/2015; 10(4):e0123068. DOI:10.1371/journal.pone.0123068 · 3.53 Impact Factor
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    ABSTRACT: In melanoma, both the induction of immunosuppression by tumor cells and the inflammatory antitumor response can induce an upregulation of counter-regulatory mechanisms such as indoleamine 2,3-dioxygenase (IDO), programmed death-ligand 1 (PD-L1) and CTLA-4C regulatory T-cells (Tregs) in the tumor microenvironment. Even though these immunosuppressive mediators are targets for immunotherapy, research investigating their expression in the peripheral blood is lacking. We therefore, performed flow cytometry on PBMCs of stage I–IV melanoma patients. IDO expression was detected in plasmacytoid dendritic cells (pDC) and monocytic myeloid-derived suppressor cells (mMDSC), and increased in advanced disease stage (p D 0.027). Tryptophan breakdown confirmed the functional activity of IDO and was linked with increased PD-L1C cytotoxic T-cells (p D 0.009), relative lymphopenia (p D 0.036), and a higher mDC/pDC ratio (p D 0.002). High levels of circulating PD-L1C cytotoxic T-cells were associated with increased CTLA-4 expression by Tregs (p D 0.005) and MDSC levels (p D 0.033). This illustrates that counter-regulatory immune mechanisms in melanoma should be considered as one interrelated signaling network. Moreover, both increased PD-L1C T-cells and CTLA-4 expression in Tregs conferred a negative prognosis, indicating their in vivo relevance. Remarkably, circulating CTLA-4, IDO, and pDC levels were altered according to prior invasion of the sentinel lymph node and IDO expression in the sentinel was associated with more IDOC PBMCs. We conclude that the expression of IDO, PD-L1, and CTLA-4 in the peripheral blood of melanoma patients is strongly interconnected, associated with advanced disease and negative outcome, independent of disease stage. Combination treatments targeting several of these markers are therefore likely to exert a synergistic response.
    OncoImmunology 04/2015; 4(3). DOI:10.4161/2162402X.2014.982382 · 6.28 Impact Factor
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    ABSTRACT: Hintergrund: Die akute Rhinosinusitis ist eine häufige entzündliche Erkrankung der Nasen- und Nasennebenhöhlenschleimhaut, die mit einer erheblichen Morbidität und sozioökonomischen Belastung verbunden ist. Ein neues Phytotherapeutikum auf Basis eines Trockenextrakts aus der Kombination von fünf Arzneipflanzen (Sinupret® extract Dragees) wurde in einer konfirmatorischen Studie an Patienten mit akuter viraler Rhinosinusitis geprüft. Methoden: 386 Patienten mit einer symptomatischen akuten viralen Rhinosinusitis wurden in einer doppelblinden, randomisierten, placebokontrollierten klinischen Prüfung 15 Tage lang mit dem Phytotherapeutikum (tägliche Dosierung 3 × 160 mg) oder mit Placebo behandelt. Primäres Zielkriterium war die von den Prüfern bewertete Restsymptomatik bei Therapieende (Major Symptom Score, MSSINV). Ergebnisse: Die Behandlung mit dem Phytotherapeutikum führte zu einer statistisch signifikanten, klinisch relevanten Verbesserung der Restsymptomatik (2,07 ± 0,18 [SEM] versus 3,47 ± 0,28 Scorepunkte, p = 0,0001; PP: N = 300) gegenüber Placebo an Visite 5. Die Anzahl der notwendigen Behandlungen (Number Needed to Treat, NNT) für die Genesung lag bei 7 (Per Protocol Population, PP). Unter Verum entwickelten 9,8% der Patienten unerwünschte Ereignisse, unter Placebo 14,1%. Schwerwiegende unerwünschte Ereignisse wurden nicht beobachtet. Die Verträglichkeit des Phytotherapeutikums wurde von den Prüfern überwiegend mit „gut“ beziehungsweise „sehr gut“ bewertet (Verum: 96,4%, Placebo: 95,3%). Schlussfolgerung: Die Ergebnisse belegen die Wirksamkeit und Verträglichkeit des Phytotherapeutikums in der Indikation akute virale Rhinosinusitis. Insbesondere aufgrund der günstigen Nutzen-Risiko-Relation eignet sich das Präparat als therapeutische Alternative.
    MMW Fortschritte der Medizin 04/2015; 157(S4):6-11. DOI:10.1007/s15006-015-2934-4
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    ABSTRACT: Introduction: Effective pharmacologic treatment exists for most patients suffering from allergic rhinitis (AR). However, both in clinical trials and in real-life studies, many patients are dissatisfied with treatment. Physicians often use multiple therapies, in an attempt to improve symptom control, often with limited evidence of success. Novel treatment options are needed and must consider unmet medical needs. Areas covered: This article reviews the clinical data for a new AR treatment. MP29-02 (Dymista®, Meda, Solna, Sweden) contains azelastine hydrochloride (AZE) and fluticasone propionate (FP), in a novel formulation and delivered in an improved device as a single nasal spray. It has shown superior efficacy in AR patients than either commercially available AZE or FP monotherapy for both nasal and ocular symptom relief, regardless of disease severity. MP29-02 also provided more effective and rapid symptom relief than either AZE or FP monotherapy delivered in the MP29-02 formulation and device. However, the effect was less than that observed versus commercial comparators, suggesting the impact of formulation and device on clinical efficacy. Expert opinion: MP29-02 simplifies AR management, surpassing the efficacy of gold standard treatment, intranasal corticosteroids (INS), for the first time. It is indicated for the treatment of moderate-to-severe seasonal allergic rhinitis and perennial allergic rhinitis when monotherapy with either intranasal antihistamine or INS is NOT considered sufficient. Most patients present with moderate/severe disease, with evidence of current or previous treatment insufficiency. MP29-02 should be the treatment of choice for these patients.
    Expert Opinion on Pharmacotherapy 03/2015; 16(6):1-16. DOI:10.1517/14656566.2015.1020789 · 3.09 Impact Factor
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    ABSTRACT: Purpose Chronic rhinosinusitis with nasal polyps (CRSwNP), a mainly Th2 cytokine-mediated disease, often involves mucus secretion. Recent evidence suggests that transmembrane protein 16A (TMEM16A), a calcium-activated Cl- channel (CaCC), can regulate mucus secretion from airway epithelium by transepithelial electrolyte transport and hydration. However, the role of TMEM16A in mucin production/secretion in the airway epithelium is not clear. This study was conducted to determine the role of TMEM16A in mediating mucin secretion in human nasal polyp epithelial cells (HNPECs) induced by IL-13. Methods Human sinonasal mucosa tissue and dissociated sinonasal epithelium from control subjects and patients with CRSwNP were assessed for the expression of TMEM16A and the secretion of human mucin 5AC (MUC5AC) by immunohistochemistry, Western blot analysis, and enzyme-linked immuno-sorbent assay (ELISA). A model of the Th2 inflammatory environment was created by exposure of primary air-liquid interface (ALI)-cultured HNPECs to interleukin-13 (IL-13) for 14 days, with subsequent assessment of TMEM16A expression in cell lysates by Western blotting and MUC5AC secretion in apical washings of cells by ELISA. Results The expressions of TMEM16A and MUC5AC were increased in human nasal polyp tissue and dissociated nasal polyp epithelium. TMEM16A was detected in IL-13-treated HNPECs, specifically in MUC5AC-positive cells but not in ciliated cells. IL-13 treatment increased percentages of TMEM16A-positive cells, MUC5AC-positive cells, and cells coexpressing TMEM16A/MUC5AC, the expression of TMEM16A protein, and the secretion of MUC5AC. T16Ainh-A01, a TMEM16A inhibitor, attenuated these IL-13-induced effects. Conclusions The expression of TMEM16A and MUC5AC are increased in CRSwNP, which might be a direct effect of Th2 cytokines present in the sinonasal mucosa in CRSwNP. Down-regulation of TMEM16A expression and MUC5AC secretion in HNPECs by T16Ainh-A01 indicates that TMEM16A might play an important role in mucin secretion in upper airway inflammatory diseases.
    Allergy, asthma & immunology research 03/2015; 7(4). DOI:10.4168/aair.2015.7.4.367 · 3.08 Impact Factor
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    ABSTRACT: Immunoglobulin E (IgE) can be highly elevated in the airway mucosa independently of IgE serum levels and atopic status. Mostly, systemic markers are assessed to investigate inflammation in airway disease for research or clinical practice. A more accurate but more cumbersome approach to determine inflammation at the target organ would be to evaluate markers locally. We review evidence for local production of IgE in allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP). Diagnostic and therapeutic consequences in clinical practice are discussed. We describe that the airway mucosa has the intrinsic capability to produce IgE. Moreover, not only do IgE-positive B cells reside within the mucosa, but all tools are present locally for affinity maturation by somatic hypermutation (SHM), clonal expansion, and class switch recombination to IgE. Recognizing local IgE in the absence of systemic IgE has diagnostic and therapeutic consequences. Therefore, we emphasize the importance of local IgE in patients with a history of AR or CRSwNP.
    Allergy, asthma & immunology research 03/2015; 7(4). DOI:10.4168/aair.2015.7.4.321 · 3.08 Impact Factor
  • C Bachert, G Holtappels
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    ABSTRACT: Research in immunology has brought great progress in knowledge of inflammatory processes in the last 2 decades, which also has an impact on the upper airways. Our understanding of the pathophysiology of chronic rhinosinusitis developed from a rather mechanistic point of view with a focus on narrow clefts and mucociliary clearance to the appreciation of a complex network of immunological pathways forming the basis of disease. We today differentiate various forms of inflammation, we start to understand complex immune-regulatory networks and the reasons for their failure, and have already developed innovative approaches for therapy for the most severely ill subjects. Due to this new knowledge in inflammation and remodeling processes within mucosal tissue, specifically on the key driving factors, new diagnostic tools and therapeutic approaches for chronic rhinosinusitis have developed; the differentiation of endotypes based on pathophysiological principles will be crucial for the use of innovative therapies, mostly humanized monoclonal antibodies. Several hundred of those antibodies are currently developed for various indications and will impact our speciality as well as pneumology to a great extent. © Georg Thieme Verlag KG Stuttgart · New York.
    Laryngo-Rhino-Otologie 03/2015; 94(S 01):S32-S63. DOI:10.1055/s-0034-1396870 · 0.99 Impact Factor
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    ABSTRACT: The aim of the present study was to compare the prevalence of self-reported and confirmable allergic rhinitis (AR) with positive skin prick test (SPT) results among adults living in urban and rural areas of China. Adults from a community in Beijing and a village in Baoding were selected as representative urban and rural dwellers, respectively. All eligible residents were enrolled from the population register and received a face-to-face interview using modified validated questionnaires. Equal sets of randomly selected self-reporting AR-positive and AR-negative participants who responded to the questionnaires were also investigated using skin prick tests. A total of 803 participants in the rural area and a total of 1,499 participants in the urban area completed the questionnaires, with response rates being 75.9% and 81.5% respectively. The prevalence of self-reported AR of the rural area (19.1%) was significantly higher than that of the urban area (13.5%). The elementary school of educational level increased the risk of having AR (adjusted OR=2.198, 95% CI=1.072-2.236) .The positive SPT rates among subjects with self-reported AR in the rural and urban areas were 32.5% and 53.3%, respectively; the confirmable AR prevalence of 6.2% and 7.2% among the rural and urban adults, respectively. The prevalence of confirmable AR is similar between rural and urban areas in China, although there is a higher prevalence of self-reported AR in the former.
    Allergy, asthma & immunology research 03/2015; 7(2):148-57. DOI:10.4168/aair.2015.7.2.148 · 3.08 Impact Factor
  • Bauke Pauwels, Karin Jonstam, Claus Bachert
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    ABSTRACT: Chronic rhinosinusitis (CRS) is a prevalent chronic inflammatory disease of the nasal and paranasal cavities and is known to seriously impair quality of life in affected patients. CRS appears to be a heterogeneous group of diseases with different inflammatory and remodeling patterns, suggesting that not only different clinical phenotypes but also pathophysiological endotypes occur. CRS with nasal polyps (CRSwNP) is considered a more severe phenotype, especially when associated with comorbid asthma, as patients having this condition often do not respond to conventional treatment, including topical and systemic corticosteroids or surgery. Recently, studies with biologic agents have shown various effects in severe airway disease; specifically in Th2-biased CRSwNP, these effects were very promising. The greatest challenge for the future is to define the different endotypes of CRSwNP using easily accessible biomarkers to select the patients who have the best chance of a positive therapeutic response to innovative approaches.
    Expert Review of Clinical Immunology 02/2015; 11(3):1-13. DOI:10.1586/1744666X.2015.1010517 · 3.34 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2015; 135(2):AB81. DOI:10.1016/j.jaci.2014.12.1196 · 11.25 Impact Factor
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    ABSTRACT: The efficacy of MP29-02 (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in an advanced delivery system) has been well established in controlled clinical trials. This study was designed to assess the use of MP29-02 and its effectiveness in routine clinical practice. This was a German multicenter, prospective, noninterventional study, including 1781 allergic rhinitis (AR) patients. Eligible patients (i.e., acute AR symptoms and visual analog scale [VAS] score >50 mm) were included, assigned MP29-02 at baseline, and reassessed after ∼14 days. Patients assessed symptom control using a VAS from 0 (not at all bothersome) to 100 mm (very bothersome) in the morning before MP29-02 use, on days 0, 1, 3, and 7 and after ∼ 14 days. Patients' perceived levels of disease control were assessed on day 3. The Youden index determined patient-reported VAS score cutoffs on day 3 for “well controlled” and “partly controlled.” MP29-02 reduced the VAS score from 75.4 mm (SD = 17.2) at baseline to 21.3 mm (SD = 18.3) by the last visit, a shift of 54.1 mm (SD = 24.6). One in every two patients felt their symptoms were well controlled at day 3. This perception of well-controlled symptoms at day 3 corresponded to an optimal VAS cutoff of 36 mm. On average, patients treated with MP29-02 crossed this well-controlled VAS cutoff by last visit. Similar results were found in adolescents, adults, and older adults, in those with perennial AR (PAR), seasonal AR (SAR), or PAR + SAR and in those with more and less severe disease. MP29-02 provides effective and rapid symptom control across all age groups in a real-life setting with responder rates higher than those observed in controlled clinical trials, supporting MP29-02's position as the drug of choice for the treatment for AR.
    Allergy and Asthma Proceedings 02/2015; 36(1). DOI:10.2500/aap.2015.36.3823 · 3.35 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2015; 135(2):AB238. DOI:10.1016/j.jaci.2014.12.1713 · 11.25 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2015; 135(2):AB53. DOI:10.1016/j.jaci.2014.12.1103 · 11.25 Impact Factor
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    ABSTRACT: Upper airway diseases including allergic rhinitis, chronic rhinosinusitis with or without polyps, and cystic fibrosis are characterized by substantially different inflammatory profiles. Traditionally, studies on the association of specific bacterial patterns with inflammatory profiles of diseases had been dependent on bacterial culturing. In the past 30 years, molecular biology methods have allowed bacterial culture free studies of microbial communities, revealing microbiota much more diverse than previously recognized including those found in the upper airway. At presence, the study of the pathophysiology of upper airway diseases is necessary to establish the relationship between the microbiome and inflammatory patterns to find their clinical reflections and also their possible causal relationships. Such investigations may elucidate the path to therapeutic approaches in correcting an imbalanced microbiome. In the review we summarized techniques used and the current knowledge on the microbiome of upper airway diseases, the limitations and pitfalls, and identified areas of interest for further research. Electronic supplementary material The online version of this article (doi:10.1186/s40413-014-0048-6) contains supplementary material, which is available to authorized users.
    World Allergy Organization Journal 01/2015; 8(1):3. DOI:10.1186/s40413-014-0048-6
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    ABSTRACT: Background Immune markers in the peripheral blood of melanoma patients could provide prognostic information. However, there is currently no consensus on which circulating cell types have more clinical impact. We therefore evaluated myeloid-derived suppressor cells (MDSC), dendritic cells (DC), cytotoxic T-cells and regulatory T-cells (Treg) in a series of blood samples of melanoma patients in different stages of disease.Methods Flow cytometry was performed on peripheral blood mononuclear cells of 69 stage I to IV melanoma patients with a median follow-up of 39 months after diagnosis to measure the percentage of monocytic MDSCs (mMDSCs), polymorphonuclear MDSCs (pmnMDSCs), myeloid DCs (mDCs), plasmacytoid DCs (pDCs), cytotoxic T-cells and Tregs. We also assessed the expression of PD-L1 and CTLA-4 in cytotoxic T-cells and Tregs respectively. The impact of cell frequencies on prognosis was tested with multivariate Cox regression modelling.ResultsCirculating pDC levels were decreased in patients with advanced (P¿=¿0.001) or active (P¿=¿0.002) disease. Low pDC levels conferred an independent negative impact on overall (P¿=¿0.025) and progression-free survival (P¿=¿0.036). Even before relapse, a decrease in pDC levels was observed (P¿=¿0.002, correlation coefficient 0.898). High levels of circulating MDSCs (>4.13%) have an independent negative prognostic impact on OS (P¿=¿0.012). MDSC levels were associated with decreased CD3+ (P¿<¿0.001) and CD3¿+¿CD8+ (P¿=¿0.017) T-cell levels. Conversely, patients with high MDSC levels had more PD-L1+ T-cells (P¿=¿0.033) and more CTLA-4 expression by Tregs (P¿=¿0.003). pDCs and MDSCs were inversely correlated (P¿=¿0.004). The impact of pDC levels on prognosis and prediction of the presence of systemic disease was stronger than that of MDSC levels.Conclusion We demonstrated that circulating pDC and MDSC levels are inversely correlated but have an independent prognostic value in melanoma patients. These cell types represent a single immunologic system and should be evaluated together. Both are key players in the immunological climate in melanoma patients, as they are correlated with circulating cytotoxic and regulatory T-cells. Circulating pDC and MDSC levels should be considered in future immunoprofiling efforts as they could impact disease management.
    Journal of Translational Medicine 01/2015; 13(1):9. DOI:10.1186/s12967-014-0376-x · 3.99 Impact Factor
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    ABSTRACT: The upper and lower airways are closely linked from an anatomical, histological and immunological point of view, with inflammation in one part of the airways influencing the other part. Despite the concept of global airway disease, the upper airways tend to be overlooked by respiratory physicians. We provide a clinical overview of the most important and recent insights in rhinitis and rhinosinusitis in relation to lower airway disease. We focus on the various exogenous and endogenous factors that play a role in the development and aggravation of chronic upper airway inflammation. In addition to the classical inhaled allergens or microorganisms with well-defined pathophysiological mechanisms in upper airway disease, environmental substances such as cigarette smoke, diesel exhaust particles and occupational agents affecting lower airway homeostasis have recently gained attention in upper airway research. We are only at the beginning of understanding the complex interplay between exogenous and endogenous factors like genetic, immunological and hormonal influences on chronic upper airway inflammation. From a clinical perspective, the involvement of upper and lower airway disease in one patient can only be fully appreciated by doctors capable of understanding the interplay between upper and lower airway inflammation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Thorax 01/2015; 70(4). DOI:10.1136/thoraxjnl-2014-205520 · 8.56 Impact Factor

Publication Stats

13k Citations
2,014.73 Total Impact Points


  • 2013–2015
    • Karolinska Institutet
      Solna, Stockholm, Sweden
    • Imperial College London
      Londinium, England, United Kingdom
  • 2002–2015
    • Universitair Ziekenhuis Ghent
      • Department of Neurology
      Gand, Flemish, Belgium
  • 1998–2015
    • Ghent University
      • • VIB Department of Molecular Biomedical Research (DMBR)
      • • VIB Department of Medical Protein Research
      Gand, Flemish, Belgium
    • Universitätsklinikum Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2014
    • University of Kragujevac
      Krabujevac, Central Serbia, Serbia
  • 2012
    • Celal Bayar Üniversitesi
      • Faculty of Medicine
      Saruhan, Manisa, Turkey
    • Mahidol University
      • Faculty of Medicine Siriraj Hospital
      Bangkok, Bangkok, Thailand
  • 2011
    • Universitätsmedizin Mannheim
      Mannheim, Baden-Württemberg, Germany
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2010
    • Sichuan University
      Hua-yang, Sichuan, China
  • 1987–2007
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 2006
    • Sun Yat-Sen University
      Shengcheng, Guangdong, China
    • Ludwig-Maximilians-University of Munich
      München, Bavaria, Germany
  • 2004
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
  • 2003
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
  • 2000
    • Deutsche Klinik für Diagnostik, Wiesbaden
      Wiesbaden, Hesse, Germany
    • Aarhus University Hospital
      Aarhus, Central Jutland, Denmark
  • 1991–1998
    • Heinrich-Heine-Universität Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1990
    • Universität Mannheim
      Mannheim, Baden-Württemberg, Germany