Marten Trendelenburg

Universitätsspital Basel, Bâle, Basel-City, Switzerland

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Publications (89)300.48 Total impact

  • Sophia Thanei · Marten Trendelenburg
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    ABSTRACT: Anti-C1q autoantibodies (anti-C1q) are frequently found in patients with systemic lupus erythematosus (SLE) and correlate with the occurrence of proliferative lupus nephritis. A previous study of anti-C1q in experimental lupus nephritis demonstrated an important role for FcγRs in the pathogenesis of lupus nephritis, suggesting a direct effect on phagocytes. Therefore, we developed an in vitro model to study the effect of SLE patient-derived anti-C1q bound to immobilized C1q (imC1q) on human monocyte-derived macrophages (HMDMs) obtained from healthy donors and SLE patients. HMDMs were investigated by analyzing the cell morphology, LPS-induced cytokine profile, surface marker expression, and phagocytosis rate of apoptotic Jurkat cells. Morphologically, bound anti-C1q induced cell aggregations of HMDMs compared with imC1q or IgG alone. In addition, anti-C1q reversed the effect of imC1q alone, shifting the LPS-induced cytokine release toward a proinflammatory response. FcγR-blocking experiments revealed that the secretion of proinflammatory cytokines was mediated via FcγRII. The anti-C1q-induced inflammatory cytokine profile was accompanied by a downregulation of CD163 and an upregulation of LPS-induced CD80, CD274, and MHC class II. Finally, HMDMs primed on bound anti-C1q versus imC1q alone displayed a significantly lower phagocytosis rate of early and late apoptotic cells accompanied by a reduced Mer tyrosine kinase expression. Interestingly, anti-C1q-dependent secretion of proinflammatory cytokines was similar in SLE patient-derived cells, with the exception that IL-10 was slightly increased. In conclusion, anti-C1q induced a proinflammatory phenotype in HMDMs reversing the effects of imC1q alone. This effect might exacerbate underlying pathogenic mechanisms in lupus nephritis.
    No preview · Article · Feb 2016 · The Journal of Immunology
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    ABSTRACT: Background: Functional deficiency of mannose-binding lectin (MBL) may contribute to the pathogenesis of chronic obstructive pulmonary disease. We hypothesized that specific MBL2 gene polymorphisms and circulating MBL protein levels are associated with clinically relevant outcomes in the Predicting Outcome using systemic Markers In Severe Exacerbations of COPD PROMISE-COPD cohort. Methods: We followed 277 patients with stable COPD GOLD stage II-IV COPD over a median period of 733 days (IQR 641-767) taking survival as the primary outcome parameter. Patients were dichotomized as frequent (≥2 AECOPD/year) or infrequent exacerbators. Serum MBL levels and single nucleotide polymorphisms of the MBL2 gene were assessed at baseline. Results: The MBL2-HYPD haplotype was significantly more prevalent in frequent exacerbators (OR: 3.33; 95 % CI, 1.24-7.14, p = 0.01). The median serum MBL concentration was similar in frequent (607 ng/ml, [IQR; 363.0-896.0 ng/ml]) and infrequent exacerbators (615 ng/ml, [IQR; 371.0-942.0 ng/ml]). Serum MBL was not associated with lung function characteristics or bacterial colonization in sputum. However, high serum MBL at stable state was associated with better survival compared to low MBL (p = 0.046, log rank test). Conclusions: In COPD, the HYPD haplotype of MBL2 gene is associated with frequent exacerbations and high serum MBL is linked to increased survival. The PROMISE-COPD study was registered at www.controlled-trials.com under the identifier ISRCTN99586989 .
    Full-text · Article · Dec 2015 · Respiratory Research
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    ABSTRACT: Background: Autoantibodies against monomeric C-reactive protein (anti-CRP-Ab) observed in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) were suggested to be associated with active LN and a poor response to therapy during short-term follow-up. The aim of this study was to confirm this finding and to investigate the prognostic value of anti-CRP-Ab in patients with LN during long-term follow-up. Methods: Sera of 57 SLE patients (47 women, 10 men) with biopsy proven LN and 122 healthy individuals were analyzed for the presence of anti-CRP-Ab by in-house ELISA. Anti-CRP-Ab levels were studied in relation to routine laboratory tests, urine analysis, levels of C3, C4, other immunological markers and the overall disease activity as assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The prognostic value of anti-CRP-Ab was tested in a subgroup of 29 newly diagnosed LN patients (median follow-up 5.9 years). Response to therapy at various time points was assessed with respect to baseline anti-CRP-Ab levels. At least partial response in the first/second year of treatment was considered as a "favorable outcome", while non-response, renal flare or end stage renal disease were considered as "unfavorable outcome". Results: Anti-CRP-Ab were only detected in patients with active renal disease and their levels correlated with SLEDAI (rs = 0.165, p = 0.002). The time to response was shorter in patients being anti-CRP-Ab negative at baseline compared to anti-CRP-Ab positive patients, p = 0.037. In the second year of therapy, baseline anti-CRP-Ab positivity was a significant predictor of "unfavorable outcome" (OR [95 % CI] = 15.6 [1.2-771]; p = 0.021). The predictive value of "baseline anti-CRP positivity" further increased when combined with "non-response to therapy in the first year". Baseline anti-CRP-Ab positivity was not a predictor of "unfavorable outcome" at the end of follow-up, (OR [95 % CI] = 5.5 [0.6-71.1], p = 0.169). Conclusions: Baseline serum levels of anti-CRP-Ab seem to be a strong risk factor for a composite outcome of non-response, renal flare or end stage renal disease after two years of standard treatment of LN. The response to therapy seems to be delayed in anti-CRP-Ab positive patients.
    Full-text · Article · Dec 2015 · Arthritis research & therapy
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    ABSTRACT: Objectives: Human studies on the role of mannose-binding lectin (MBL) in patients with invasive candidiasis have yielded conflicting results. We investigated the influence of MBL and other lectin pathway proteins on Candida colonization and intra-abdominal candidiasis (IAC) in a cohort of high-risk patients. Methods: Prospective observational cohort study of 89 high-risk intensive-care unit (ICU) patients. Levels of lectin pathway proteins at study entry and six MBL2 single-nucleotide polymorphisms were analysed by sandwich-type immunoassays and genotyping, respectively, and correlated with development of heavy Candida colonization (corrected colonization index (CCI) >0.4) and occurrence of IAC during a 4-week period. Results: Within 4 weeks after inclusion a CCI>0.4 and IAC was observed in 47% and 38% of patients respectively. Neither serum levels of MBL, ficolin-1,-2,-3, MASP-2 or collectin liver 1 nor MBL2 genotypes were associated with a CCI>0.4. Similarly, none of the analysed proteins was found to be associated with IAC with the exception of lower MBL levels (HR 0.74, p=0.02) at study entry. However, there was no association of MBL deficiency (<0.5 μg/ml), MBL2 haplo- or genotypes with IAC. Conclusion: Lectin pathway protein levels and MBL2 genotype investigated in this study were not associated with heavy Candida colonization or IAC in a cohort of high-risk ICU patients.
    No preview · Article · Dec 2015 · The Journal of infection
  • Sophia Thanei · Marten Trendelenburg

    No preview · Conference Paper · Sep 2015
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    Sophia Thanei · Dominique Vanhecke · Marten Trendelenburg
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    ABSTRACT: Autoantibodies against complement C1q (anti-C1q) strongly correlate with the occurrence of lupus nephritis and hypocomplementemia in systemic lupus erythematosus (SLE). Although a direct pathogenic role of anti-C1q has been suggested, the assumed complement-activating capacity remains to be elucidated. Using an ELISA-based assay, we found that anti-C1q activate the classical (CP) and lectin pathways (LP) depending on the anti-C1q immunoglobulin-class repertoire present in the patient's serum. IgG anti-C1q resulted in the activation of the CP as reflected by C4b deposition in the presence of purified C1 and C4 in a dose-dependent manner. The extent of C4b deposition correlated with anti-C1q levels in SLE patients but not in healthy controls. Our data indicate that SLE patient-derived anti-C1q can activate the CP and the LP but not the alternative pathway of complement. These findings are of importance for the understanding of the role of anti-C1q in SLE suggesting a direct link to hypocomplementemia. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Jul 2015 · Clinical Immunology
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    ABSTRACT: Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that impacts on patients quality of life. Treatment in SLE not only aims to decrease disease activity and damage accrual but also to improve health-related quality of life (HRQOL). Only few studies have examined the influence of detailed disease-related organ involvement on HRQOL Objectives To assess HRQOL and disease activity in a national Swiss multicentre cohort of patients with SLE (1;2). Methods Cross-sectional study on patients included in the Swiss SLE Cohort Study between April 2007 and June 2014. Inclusion criteria were: age ≥18 years, SLE defined by the American College of Rheumatology (ACR) classification criteria, written informed consent, having completed a Medical Outcome Study Short Form 36 (SF-36) at baseline and assessed for SLE disease activity at the same time. HRQOL was assessed with the mental component scale (MCS) and Physical component scale (PCS) and the eight subscales of the SF-36. Disease activity was assessed by the SLE Disease Activity Index score with the Safety of Estrogens in SLE National Assessment (SELENA-SLEDAI) modification physican's global assessement score (PGA). Disease damage was assessed by the System Lupus Internation Collaborating Clinics/ACR Damage Index for SLE (SLICC). Results Two hundred fifty-two patients were included in the study. The median [IQR] MCS was 46.5 [34.9 – 54.1] and the median [IQR] PCS of the SF-36 was 41.1 [33.2 – 47.3]. The median [IQR] SELENA-SLEDAI score was 3 [0.75 - 8]. Univariate analysis revealed significant correlations between PCS and PGA (r=-0.18, p<0.01), ESR (r=-0.24, p<0.001), hemoglobin (r=0.16, p<0.05), steroid intake (r=-0.25, p<0.0001), immunosuppressive treatment intake (r=-0.20, p<0.01), age (r=-0.23, p<0.001), body mass index (r=-0.17, p<0.05), and SLICC (r=-0.24, p<0.001), tobacco status (r=0.16, p<0.05). Significant correlations were found between MCS and PGA (r=-0.15, p<0.05), SELENA-SLEDAI (r=-0.22, p<0.0001), and ESR (r=-0.14, p<0.05). SELENA-SLEDAI inversely correlated with MCS (r=-0.22; p<0.001), role physical (RP) (r=-0.26; p<0.0001), bodily pain (BP) (r=-0.23; p<0.001), vitality (VT) (r=-0.15; p<0.05), social function (SF) (r= -0.14; p<0.05), social function (SF) (r=-0.14; p<0.05), role emotional (RE) (r=-0.28; p<0.0001), and mental health (MH) (r=-0.17; p<0.05). Musculoskeletal and renal involvements were the two dimensions of the SELENA-SLEDAI that correlate the most with SF-36 scores. SLICC inversely correlated with PCS (-0.24; p<0.001), physical functionning (PF) (r=-0.21; p<0.01), RP (r=-0.14; p<0.05), and BP (r=-0.15; p<0.05). Diabetes was the dimension of the SLICC that correlates the most with SF-36 scores. Conclusions Health-related quality of life is low in Swiss SLE patients, particularly in those with musculoskelettal and renal involvement or diabetes. References Disclosure of Interest None declared
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
  • Mihaela Stegert · Merete Bock · Marten Trendelenburg
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    ABSTRACT: Hereditary human C1q deficiency has been well described to be associated with high susceptibility for the development of systemic lupus erythematosus (SLE). The majority of subjects present a clinical syndrome closely related to SLE. However, limited information is available about the primary diagnosis and particular clinical manifestations of SLE in this specific subgroup of patients. In this review, we performed a comprehensive search of electronic databases up to November 2014 to identify and analyze reports on patients with C1q deficiency. We identified 71 C1q-deficient patients descending from 45 families that had been published. According to the American College of Rheumatology (ACR) diagnostic criteria for SLE 39/71 (55%) subjects could be classified as having SLE. Another 16/71 (22.5%) presented a SLE-like syndrome (defined as 3 positive ACR criteria) whereas in 16/71 (22.5%) no SLE could be diagnosed at time of publication. Symptoms began at a median age of 5 years, male and females being equally affected. Discoid rash (56% versus 10%, p<0.001) and oral ulcers (49% versus 24%, p<0.001) occurred significantly more frequent in C1q deficiency-associated SLE/SLE-like disease than in sporadic SLE, whereas arthritis (38% versus 84%, p<001) and anti-ds-DNA (18% versus 78%, p<0.001) occurred less frequently. Renal and neurological manifestations were found to occur similarly frequent. The severe course of disease in some patients seemed to be mostly due to severe infections at early ages and not in particular due to more aggressive SLE manifestations. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Apr 2015 · Molecular Immunology

  • No preview · Conference Paper · Oct 2014
  • Kf Koenig · C Ribi · M Radosavac · H Zulewski · M Trendelenburg
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    ABSTRACT: Objectives: Systemic lupus erythematosus (SLE) is associated with considerable cardiovascular morbidity that has not yet been directly compared with other diseases with known cardiovascular risk. Methods: Two hundred and forty-one patients of the multicentre Swiss SLE cohort study (SSCS) were cross-sectionally assessed for coronary heart disease (CHD), cerebrovascular disease (CVD) and peripheral artery disease (PAD). SLE patients were compared with a cohort of 193 patients with type-1 diabetes mellitus being followed at the University Hospital Basel. A subgroup analysis of 50 age- and sex-matched patients from the University Hospital Basel was performed. Results: Of patients within the SSCS 13.3% had one or more vascular events: 8.3% CHD, 5% CVD and 1.2% PAD. In type-1 diabetes mellitus patients, 15% had vascular events: 9.3% CHD, 3.1% CVD and 5.6% PAD. In the matched subgroup, 26% of SLE patients had vascular events (14% CHD) compared with 12% in type-1 DM patients (2% CHD). Cardiovascular risk factors were similar in both groups. Vascular events in SLE patients were associated with age, longer disease duration, dyslipidaemia, and hypertension. Conclusion: Cardiovascular morbidity in SLE is at least as frequent as in age- and sex-matched type-1 diabetes mellitus patients. Therefore, aggressive screening and management of cardiovascular risk factors should be performed.
    No preview · Article · Sep 2014 · Lupus
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    ABSTRACT: The role of complement has been demonstrated in experimental models of neuromyeltis optica (NMO), however, only few studies have analysed complement components longitudinally in NMO patients. We measured serum or plasma concentrations of anti-C1q antibodies and complement split products C3a, C4a and soluble C5b-9 in patients with NMO, multiple sclerosis and healthy controls. NMO patients had higher levels of C3a and anti-C1q antibodies than healthy controls. C3a levels correlated with disease activity, neurological disability and aquaporin-4 IgG in NMO patients suggesting a role of the alternative pathway of complement in the pathogenesis of NMO and supporting the strategy of therapeutic complement inhibition.
    Full-text · Article · Sep 2014 · Journal of Neuroimmunology
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    Full-text · Dataset · Aug 2014
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    ABSTRACT: OBJECTIVES: To describe disease characteristics and treatment modalities in a multidisciplinary cohort of systemic lupus erythematosus (SLE) patients in Switzerland. METHODS: Cross-sectional analysis of 255 patients included in the Swiss SLE Cohort and coming from centres specialised in Clinical Immunology, Internal Medicine, Nephrology and Rheumatology. Clinical data were collected with a standardised form. Disease activity was assessed using the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), an integer physician's global assessment score (PGA) ranging from 0 (inactive) to 3 (very active disease) and the erythrocyte sedimentation rate (ESR). The relationship between SLE treatment and activity was assessed by propensity score methods using a mixed-effect logistic regression with a random effect on the contributing centre. RESULTS: Of the 255 patients, 82% were women and 82% were of European ancestry. The mean age at enrolment was 44.8 years and the median SLE duration was 5.2 years. Patients from Rheumatology had a significantly later disease onset. Renal disease was reported in 44% of patients. PGA showed active disease in 49% of patients, median SLEDAI was 4 and median ESR was 14 millimetre/first hour. Prescription rates of anti-malarial drugs ranged from 3% by nephrologists to 76% by rheumatologists. Patients regularly using anti-malarial drugs had significantly lower SELENA-SLEDAI scores and ESR values. CONCLUSION: In our cohort, patients in Rheumatology had a significantly later SLE onset than those in Nephrology. Anti-malarial drugs were mostly prescribed by rheumatologists and internists and less frequently by nephrologists, and appeared to be associated with less active SLE.
    Full-text · Article · Aug 2014 · Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology
  • Marten Trendelenburg
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    ABSTRACT: Complement is part of the innate immune system and underlies one of the main effector mechanisms of antibody-mediated immunity. Among its physiological activities, complement mediates the disposal of immune complexes and the products of inflammatory injury. Accordingly, low levels of complement suggesting ongoing complement activation and consumption are a well-known phenomenon in patients with cryoglobulinemia. The consumption of complement components in serum is paralleled by the deposition of complement in affected tissues such as the kidney. Experimental data suggest that complement activation is a major factor explaining the inflammatory organ damage seen in cryoglobulinemia in vivo. However, more studies are required to clarify the pathogenic role of complement in cryoglobulinemia.
    No preview · Article · Apr 2014
  • Jürg A. Schifferli · Marten Trendelenburg
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    ABSTRACT: Cryoglobulinemia was identified and named many years ago by clinicians who related the in vitro precipitation of globulins from serum incubated in the cold with diseases. One major point was that there was no evidence for a known disease in many patients with mixed cryoglobulins. Thus, the terminology mixed essential cryoglobulinemia became accepted. The discovery of HCV as the causative agent of mixed essential cryoglobulinemia allowed not only the introduction of a new nomenclature (largely removing the designation essential), but studies of the relationship between this viral disease and the emergence of pathological clones of B cells.
    No preview · Article · Apr 2014
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    Michael Osthoff · Marten Trendelenburg
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    ABSTRACT: Contrast-induced nephropathy (CIN) is the third leading cause of acute renal failure in hospitalized patients. Endothelial dysfunction, renal medullary ischemia, and tubular toxicity are regarded as the most important factors in the pathogenesis of CIN. Mannose-binding lectin (MBL), a pattern recognition protein of the lectin pathway of complement, has been found to aggravate and mediate tissue damage during experimental renal ischemia/reperfusion (I/R) injury which was alleviated by inhibition with C1 inhibitor, a potent MBL, and lectin pathway inhibitor. In this paper, we highlight the potential role of MBL in the pathogenesis of human CIN. In experimental I/R models, MBL was previously found to induce tubular cell death independent of the complement system. In addition, after binding to vascular endothelial cells, MBL and its associated serine proteases were able to trigger a proinflammatory reaction and contribute to endothelial dysfunction. In humans, urinary MBL was increased after administration of contrast media and in individuals with CIN. Moreover, individuals with normal/high MBL levels were at increased risk to develop radiocontrast-induced renal dysfunction. Hence, MBL and the lectin pathway seem to be a promising target given that a licensed, powerful, human recombinant inhibitor exits to be added to the scarce armamentarium currently available for prophylaxis of CIN.
    Preview · Article · Dec 2013
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    ABSTRACT: Functional deficiency of mannan-binding lectin (MBL) has been associated with adverse pregnancy outcome. Adverse events during pregnancy have also been described in women with autoimmune thyroid diseases (AITD), and thyroid hormones have been shown to influence serum levels of MBL. Therefore, the aim of this study was to analyse the impact of MBL-deficiency on the outcome of pregnancy in relation to the presence of AITD. Almost one year after delivery, we assessed serum MBL levels and MBL2-genotypes in 212 women positively screened for AITD in pregnancy. In 103 of these women, we could also measure MBL levels in frozen serum samples from the 9-12(th) gestational week, obtaining 96 pairs of MBL values (pregnancy vs. follow-up). As controls, 80 sera of pregnant women screened negatively for AITD were used. MBL2-genotyping was performed using multiplex PCR. Women with thyroid dysfunction and/or thyroid peroxidase antibodies (TPOAb) had lower MBL levels during pregnancy than controls, (3275 vs. 5000 ng/ml, p<0.05). The lowest levels were found in women with elevated thyroid-stimulating hormone (TSH) levels in the absence of TPOAb (2207 ng/ml; p<0.01 as compared to controls). MBL2 genotype distribution did not differ between subgroups. At a median follow-up period of 17 months (range: 3-78 months) after delivery, median MBL level had decreased further to 1923 ng/ml (p<0.0001) without significant changes in TSH. In an explorative survey, functional MBL-deficiency was neither linked to a history of spontaneous abortion, nor other obstetric complications, severe infections throughout life/pregnancy or antibiotics use in pregnancy. In conclusion, hypothyroidism during pregnancy is associated with decreased MBL levels, and the levels decreased further after delivery.
    Full-text · Article · Dec 2013 · PLoS ONE
  • S. Thanei · D. Vanhecke · C. Ploix · M. Trendelenburg

    No preview · Article · Dec 2013 · Molecular Immunology
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    Merete Bock · Ingmar Heijnen · Marten Trendelenburg
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    ABSTRACT: In cross-sectional studies autoantibodies against complement C1q (anti-C1q) were found to be highly associated with active lupus nephritis. The aim of this retrospective study was to determine the value of anti-C1q as follow-up marker of disease activity and renal involvement in patients with systemic lupus erythematosus (SLE). Fifty-two patients with SLE and a minimum of three anti-C1q measurements during follow-up were analyzed. Anti-C1q levels correlated with global disease activity scores. In subgroup analyses, patients without renal involvement did not show a significant correlation between anti-C1q levels and disease activity. In contrast, in patients with renal involvement, anti-C1q levels correlated well with global disease activity. In addition, a positive correlation with the urine protein-to-creatinine ratio and anti-dsDNA antibody levels as well as a negative correlation with complement levels was observed. Anti-C1q antibodies were found to strongly correlate with parameters of SLE disease activity during follow-up, in particular with regard to renal involvement.
    Preview · Article · Dec 2013 · Molecular Immunology

  • No preview · Article · Dec 2013 · Molecular Immunology

Publication Stats

1k Citations
300.48 Total Impact Points

Institutions

  • 1999-2015
    • Universitätsspital Basel
      • • Klinik für Infektiologie & Spitalhygiene
      • • Klinik für Innere Medizin
      Bâle, Basel-City, Switzerland
  • 2013
    • Inselspital, Universitätsspital Bern
      Berna, Bern, Switzerland
  • 2000-2013
    • Universität Basel
      • Department of Biomedicine
      Bâle, Basel-City, Switzerland
  • 2003-2005
    • Imperial College London
      • • Faculty of Medicine
      • • Imperial College Clinical Imaging Facility
      Londinium, England, United Kingdom
  • 2001-2003
    • University of Bergen
      Bergen, Hordaland, Norway
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
    • University of Milan
      • Department of Internal Medicine
      Milano, Lombardy, Italy