Søren Jacobsen

Copenhagen University Hospital, København, Capital Region, Denmark

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Publications (166)663.96 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: We investigated the antibody levels against early antigens of Epstein–Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV6) in systemic lupus erythematosus (SLE) patients and healthy controls, and further correlated these antibodies to haematology/biochemistry, serology, and disease activity measures. Method: Immunoglobulin (Ig)M, IgG, and IgA levels against the DNA polymerase processivity factors of EBV, CMV, and HHV6, termed early antigen diffuse (EA/D), pp52, and p41, respectively, were determined in plasma samples from 77 SLE patients and 29 healthy controls by using enzyme-linked immunosorbent assays (ELISAs). Results: IgM, IgG, and IgA levels against EBV EA/D, and IgG and IgA levels against CMV pp52, were significantly higher in SLE patients compared with healthy controls. Furthermore, EBV EA/D- and CMV pp52-directed IgG levels were inversely and positively associated, respectively, with lymphocyte counts in SLE patients. None of the findings seemed to be associated with use of immunosuppressive medication. Conclusions: Our results suggest strong, but opposite, associations of lytic EBV and CMV infections with SLE. The amplified humoral responses to EBV EA/D and CMV pp52 in our SLE patient cohort probably reflect aberrant control of EBV and CMV reactivation. However, reactivation of EBV appeared to correlate with lymphopenic manifestations in SLE patients whereas CMV reactivation seemed to correlate with increments in lymphocyte levels.
    Scandinavian Journal of Rheumatology 01/2015; 44(2). DOI:10.3109/03009742.2014.973061 · 2.61 Impact Factor
  • L Dreyer, S Jacobsen, L Juul, L Terslev
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    ABSTRACT: We aimed to determine 1) ultrasound (US) abnormalities in patients with systemic lupus erythematosus (SLE) with and without hand arthralgia at the day of examination compared with clinical evaluation and healthy controls, and 2) inter-observer reliability of the US abnormalities. Thirty-three female SLE patients were twice examined with US by three trained examiners. Using B-mode and Doppler US, unilateral wrist and metacarpophalangeal (MCP) joints were examined for synovitis and erosions as well as signs of hand tenosynovitis using a GE Logiq 9 US machine with Doppler settings for slow flow. All patients also underwent clinical joint evaluation and were compared with 11 healthy controls (HC). Among the patients with SLE 16 (48%) had signs of wrist synovitis, which was only observed in one HC (p = 0.03). Corresponding figures for any MCP joint were 12 (36%) and 0 (p = 0.06). In SLE patients, 18% had hand tenosynovitis and 6% bone erosions. Wrist synovitis was detected by US in 16 SLE patients (81%) with arthralgia compared with 17 patients without (18%) (p = 0.0005). Any US abnormalities were observed in 44% of 25 wrists without tenderness at clinical examination and in 46% of 26 wrists without swelling. Corresponding percentages for MCP2 joints were 27% and 21%. Inter-observer reliability of the US findings was good to excellent for examination of hand joints and tendons. A majority of SLE patients with hand arthralgia showed US signs of synovitis, erosions and tenosynovitis indicating subclinical disease. Even SLE patients without clinical signs of joint inflammation demonstrated US abnormalities. Good to excellent inter-observer reliability was found in US evaluation of hands in patients with SLE. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
    Lupus 12/2014; DOI:10.1177/0961203314561666 · 2.48 Impact Factor
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    ABSTRACT: To evaluate the expression profile of cell-free circulating microRNA (miRNA) in systemic sclerosis (SSc), healthy controls (HC), and systemic lupus erythematosus (SLE).
    The Journal of Rheumatology 11/2014; 42(2). DOI:10.3899/jrheum.140502 · 3.17 Impact Factor
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    ABSTRACT: Objectives To determine the occurrence of traditional cardiovascular (CV) risk factors and coronary artery calcification (CAC) in adults with polymyositis (PM) or dermatomyositis (DM) compared to healthy controls and to assess the association between CV risk factors, PM/DM and CAC score.Methods In a cross-sectional, observational study of 76 patients with PM/DM and of 48 gender- and age- matched healthy controls traditional CV risk factors were assessed. CAC was quantified by means of cardiac CT scan and expressed in Agatston units (U). The associations between CV risk factors, PM/DM and CAC were studied by multivariate analyses.ResultsThirty-three percent of the patients were obese compared to 11% of the controls (P = 0.005). Hypertension and diabetes were more frequent in patients (71 % vs. 42%, P = 0.002 and 13% vs. 0%, P = 0.007) and patients had higher levels of triglycerides (P = 0.0009). High CAC score occurred more frequently in patients (20% vs. 4%, P = 0.04). In multivariate analysis of patients factors associated with CAC were age (P = 0.02) and smoking (P = 0.02).Conclusion In this study, traditional CV risk factors and severe CAC were commonly found in patients with PM/DM. However, severe CAC was not associated with PM/DM per se, but rather with age and smoking in these patients. This article is protected by copyright. All rights reserved.
    11/2014; DOI:10.1002/acr.22520
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    ABSTRACT: Objectives: To determine to what extent shared epitopes, smoking, and anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with disease activity and erosive disease in patients with rheumatoid arthritis (RA) at disease onset. Method: RA patients not previously treated with disease-modifying anti-rheumatic drugs (DMARDs) and with a disease duration of < 6 months (CIMESTRA study) were examined for shared epitopes, anti-CCP antibodies, immunoglobulin M rheumatoid factor (IgM-RF) and IgA-RF, radiographic erosive changes in hands and feet, and clinical disease activity. Results: The study comprised 153 patients, of whom 104 (68%) were ever-smokers. The prevalence of patients with 0, 1, or 2 shared epitopes was 40 (48%), 71 (49%), and 33 (23%), respectively. Anti-CCP antibodies, IgM-RF, and IgA-RF were present in 89 (58%), 99 (65%), and 82 (54%) patients, respectively. Among smokers, erosive disease was associated with anti-CCP antibodies [odds ratio (OR) 3.9, 95% confidence interval (CI) 1.6-9.3], IgM-RF (OR 4.9, 95% CI 1.9-12), and IgA-RF (OR 2.8, 95% CI 1.2-6.4) but absent with regard to shared epitopes. Among never-smokers, erosive disease was not associated with either shared epitopes or antibodies. All antibody levels measured were associated with smoking and shared epitopes. Conclusions: Shared epitopes and smoking were associated with the production of anti-CCP antibodies and rheumatoid factors of IgM and IgA isotypes, which again were associated with erosive disease at presentation only in smokers. As shared epitopes and smoking were not directly associated with erosive disease, smoking may enhance the development of erosive disease in RA at different levels or through separate pathways.
    Scandinavian Journal of Rheumatology 09/2014; 44(1):1-5. DOI:10.3109/03009742.2014.918651 · 2.61 Impact Factor
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    ABSTRACT: OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. RESULTS: Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8-4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7-5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2-5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9-6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5-5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3-4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8-38.4, p < 0.01). CONCLUSIONS: Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
    Lupus 08/2014; DOI:10.1177/0961203314547791 · 2.48 Impact Factor
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    ABSTRACT: The complement system plays a pathophysiological role in systemic lupus erythematosus (SLE). This study aims to investigate whether an association exists between the ficolins that are part of the lectin complement pathway and SLE. EDTA plasma samples from 68 Danish SLE patients and 29 healthy donors were included in the study. Plasma concentrations of Ficolin-1, -2, and -3 were determined in specific sandwich ELISAs. Lectin pathway activity via Ficolin-3 was measured in ELISA on acetylated bovine serum albumin (acBSA) and measured as Ficolin-3 binding and deposition of C4, C3 and the terminal complement complex (TCC). SLE patients had increased levels of Ficolin-3, 21.6μg/ml as compared to 17.0μg/ml in healthy controls (P=0.0098). The Ficolin-1 plasma concentration was negatively correlated with SLE Disease Activity Index (SLEDAI) (Rho=-0.29, P=0.015) and positively correlated to the [Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index] (SDI) (Rho=0.27, P=0.026). The Ficolin-1 concentration was also associated with the occurrence of arterial (P=0.0053) but not venous thrombosis (P=0.42). Finally, deposition of C4, C3 and TCC in the Ficolin-3 pathway were all correlated to SLEDAI, respectively (P<0.0076). The Ficolin-1 association to SLEDAI and SDI as well as arterial thrombosis shown in this study suggests that Ficolin-1 may be a potential new biomarker for patients with SLE. Furthermore, Ficolin-3 mediated complement activation may be valuable in monitoring disease activity in SLE patients due to the high sensitivity for complement consumption in the assay independent of the Ficolin-3 concentration.
    Molecular Immunology 07/2014; 63(2). DOI:10.1016/j.molimm.2014.07.003 · 3.00 Impact Factor
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    ABSTRACT: A woman with systemic lupus erythematosus (SLE) and lupus nephritis had two pregnancies which both resulted in complications known to be associated with SLE, i.e. late abortion, preterm delivery and pre-eclampsia. We conclude that disease quiescence is important for a successful outcome and that pregnant women with SLE should be followed in a multidisciplinary setting.
    Ugeskrift for laeger 07/2014; 176(29).
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    ABSTRACT: Tocilizumab (TCZ), a monoclonal antibody targeting the human interleukin-6-receptor (IL-6R), is indicated for the treatment of rheumatoid arthritis (RA). We examined whether three IL6R single-nucleotide polymorphisms rs12083537, rs2228145 (formerly rs8192284), and rs4329505 with previously reported functional effects were associated with clinical response to TCZ in a retrospective study cohort consisting of 79 RA patients. Three months after initiation of TCZ therapy, changes in swollen joint count (SJC) and, subordinately, tender joint count (TJC), serum-CRP, DAS28-CRP, and EULAR-response were tested for association with the IL6R-haplotype or genotype. The major allele (A) of rs12083537 and the minor allele (C) of rs4329505 were associated with a poor SJC response (P=0.02 and 0.02, respectively). Moreover, the AAC-haplotype (for rs12083537, rs2228145, and rs4329505, respectively) was associated with a poor SJC response (P=0.00004) and, with borderline significance, EULAR-response (P=0.05). These data suggest that genetic variation in IL6R may aid in predicting TCZ therapy outcome in RA patients.
    Pharmacogenetics and Genomics 06/2014; 24(8). DOI:10.1097/FPC.0000000000000071 · 3.45 Impact Factor
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    ABSTRACT: Several studies indicate a role for toll-like receptors (TLRs) in the pathogenesis of systemic lupus erythematosus (SLE). We aimed to investigate the risk of SLE and typical clinical and serological manifestations of SLE potentially conferred by selected single nucleotide polymorphisms (SNPs) of genes encoding TLR7, TLR8, and TLR9. Using a multiplexed bead-based assay, we analyzed eight SNPs in a cohort of 142 Danish SLE patients and a gender-matched control cohort comprising 443 individuals. Our results showed an association between the rs3853839 polymorphism of TLR7 and SLE (G vs. C, P = 0.008, OR 1.60, 95 % CI 1.12-2.27 in females; P = 0.02, OR 4.50, 95 % CI 1.18-16.7 in males) confirming recent findings in other populations. Additionally, an association between the rs3764879 polymorphism of TLR8 and SLE (G vs. C, P < 0.05, OR 1.36, 95 % CI 0.99-1.86 in females; P = 0.06, OR 4.00, 95 % CI 0.90-17.3 in males) was found. None of the other investigated SNPs were associated with SLE but several SNPs were associated with clinical and serological manifestations. In summary, a previously shown association between the rs3853839 SNP of TLR7 and SLE in Asian patients was also found in Danish patients. Together with the association of several other SNPs of TLR8 and TLR9 with various clinical and serological manifestations of SLE these findings corroborate the pathogenic significance of TLRs in SLE.
    Molecular Biology Reports 06/2014; 41(9). DOI:10.1007/s11033-014-3447-4 · 1.96 Impact Factor
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    ABSTRACT: Simple measures of type I interferon (IFN) activity constitute highly attractive biomarkers in systemic lupus erythematosus (SLE). We explore galectin-3-binding protein (G3BP) as a novel measure of type I IFN activity and serum/plasma biomarker in large independent cohorts of patients with SLE and controls. Serum and plasma G3BP concentrations were quantified using ELISA. Type I IFN activity was assessed by Mx1 reporter gene expression assays and correlated to serum G3BP concentrations (SLE-IFN-α, n=26 and healthy controls (HCs), n=10). Plasma G3BP concentrations in the SLE-Denmark (DK) (n=70) and SLE-Sweden (SE) (n=68) cohorts were compared with the HC-DK (n=47) and HC-SE (n=50) cohorts and patients with systemic sclerosis (n=111). In 15 patients with SLE, serum G3BP in consecutive samples was correlated to disease activity. Correlation analysis between G3BP, clinical parameters including disease activity in the four SLE cohorts was performed. G3BP concentrations correlated significantly with the IFN-α reporter gene assay (r=0.56, p=0.0005) and with IFN-α gene expression scores (r=0.54, p=0.0002). Plasma concentrations were significantly increased in the SLE-DK and SLE-SE cohorts compared with HCs and patients with systemic sclerosis (p<0.0001 and p=0.0009). G3BP concentrations correlated with disease activity measures in the SLE-DK- and SLE-IFN-α cohorts (p=0.0004 and p=0.05) but not in the SLE-SE cohort (p=0.98). Markedly temporal variation was observed in G3BP levels in the consecutive SLE-samples and was significantly associated with changes in disease activity (r=0.44, p=0.014). G3BP plasma levels reflect type I IFN activity and are increased in SLE. Associations with disease activity or clinical manifestations are uncertain. This study highlights G3BP as a convenient measure of type I IFN-dependent gene activation.
    06/2014; 1(1):e000026. DOI:10.1136/lupus-2014-000026
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    ABSTRACT: The principle of treating-to-target has been successfully applied to many diseases outside rheumatology and more recently to rheumatoid arthritis. Identifying appropriate therapeutic targets and pursuing these systematically has led to improved care for patients with these diseases and useful guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology, dermatology, internal medicine and clinical immunology, and a patient representative, contributed to this initiative. The majority convened on three occasions in 2012-2013. Twelve topics of critical importance were identified and a systematic literature review was performed. The results were condensed and reformulated as recommendations, discussed, modified and voted upon. The finalised bullet points were analysed for degree of agreement among the task force. The Oxford Centre level of evidence (LoE, corresponding to the research questions) and grade of recommendation (GoR) were determined for each recommendation. The 12 systematic literature searches and their summaries led to 11 recommendations. Prominent features of these recommendations are targeting remission, preventing damage and improving quality of life. LoE and GoR of the recommendations were variable but agreement was >0.9 in each case. An extensive research agenda was identified, and four overarching principles were also agreed upon. Treat-to-target-in-SLE (T2T/SLE) recommendations were developed by a large task force of multispecialty experts and a patient representative. It is anticipated that 'treating-to-target' can and will be applicable to the care of patients with SLE.
    Annals of the rheumatic diseases 04/2014; DOI:10.1136/annrheumdis-2013-205139 · 9.27 Impact Factor
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    ABSTRACT: This study aimed to demonstrate possible associations between genetic polymorphisms in Toll-like receptor 3, interferon induced with helicase C domain 1 (IFIH1) and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 and systemic lupus erythematosus (SLE), including the phenotypes lupus nephritis and malar rash, as well as the presence of autoantibodies against nucleic acid-containing complexes. Genotyping was carried out in two Danish cohorts [Copenhagen (CPH) and Odense (ODE)] totaling 344 patients and was compared with 641 previously genotyped healthy controls. In the ODE cohort, the patients were only genotyped for the rs1990760 polymorphism of IFIH1. Single nucleotide polymorphisms (SNPs) were determined by a multiplex bead-based assay (CPH cohort) or real-time PCR (ODE cohort). Associations were investigated using the Cochran-Armitage trend test. The odds ratio (OR) for minor allele homozygotes versus major allele homozygotes suggested a protective effect of the IFIH1 rs1990760 SNP for SLE in the ODE cohort [OR 0.52, 95 % confidence intervals (95 % CI) 0.31-0.88, Pcorr. = 0.05] but not in the CPH cohort, although the OR suggested a trend in the same direction, and when combining the two patient cohorts, ORs were 0.57, 95 % CI 0.37-0.88. None of the other investigated polymorphisms showed any association with SLE. Regarding phenotypes, we found a statistically significant association between rs1990760 and malar rash in the CPH cohort, with ORs suggesting a protective effect (OR 0.28, 95 % CI 0.13-0.62 for heterozygotes and OR 0.11, 95 % CI 0.03-0.41 for homozygotes, Pcorr. = 0.0001). There were no significant associations between rs1990760 and presence of anti-dsDNA, anti-U1RNP, or anti-Smith antibodies. Our study supports previous findings of an association between the rs1990760 polymorphism of IFIH1 and SLE and indicates that this SNP may also be associated with malar rash in SLE patients although this finding needs confirmation.
    Rheumatology International 04/2014; 34(10). DOI:10.1007/s00296-014-3012-4 · 1.63 Impact Factor
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    ABSTRACT: Despite anti-dsDNA antibodies constitute a wide range of specificities, they are considered as the hallmark for systemic lupus erythematosus (SLE).
    04/2014; 1(1):e000007. DOI:10.1136/lupus-2013-000007
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    ABSTRACT: Epstein-Barr virus (EBV) has for long been associated with systemic lupus erythematosus (SLE). In this study, we investigated the levels of latent and lytic antigen EBV-specific T-cells and antibodies in SLE patients.
    04/2014; 1(1):e000015. DOI:10.1136/lupus-2014-000015
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    ABSTRACT: Objective. This study assessed the suggested association between pregnancy-associated hypertensive disorders, hyperemesis and subsequent risk of RA using a cohort with information about pre-pregnancy health.Methods. Self-reported information on pre-pregnancy health, pregnancy course, gestational hypertension, pre-eclampsia and hyperemesis was available from 55 752 pregnant women included in the Danish National Birth Cohort. Information about pregnancy-related factors and lifestyle was obtained by interviews twice during pregnancy and at 6 months post-partum. Women were followed for RA hospitalizations identified in the Danish National Patient Register. Hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards models. Women with RA and non-specific musculoskeletal problems at the time of pregnancy were excluded.Results. On average, women were followed for 11 years after childbirth and 169 cases of RA were identified. The risk of RA was increased in women with pre-eclampsia (n = 11, HR = 1.96, 95% CI 1.06, 3.63), a poor self-rated pregnancy course (n = 32, HR = 1.63, 95% CI 1.11, 2.39) and fair or poor self-rated pre-pregnancy health (fair health: n = 86, HR = 1.52, 95% CI 1.11, 2.09; poor health: n = 14, HR = 3.24, 95% CI 1.82, 5.76). Hyperemesis was not associated with risk of RA.Conclusion. We confirmed the previously suggested increased risk of RA in women with pre-eclampsia and also found an inverse association between self-rated pre-pregnancy health and risk of RA. These results suggest that the clinical onset of RA is preceded by a prolonged subclinical phase that may interfere with women's general well-being and pregnancy course or that some women carry a shared predisposition to pre-eclampsia and RA.
    Rheumatology (Oxford, England) 03/2014; 53(8). DOI:10.1093/rheumatology/keu150 · 4.44 Impact Factor
  • Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A254-A254. DOI:10.1136/annrheumdis-2013-eular.790 · 9.27 Impact Factor
  • Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A261-A262. DOI:10.1136/annrheumdis-2013-eular.811 · 9.27 Impact Factor
  • Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):539-539. DOI:10.1136/annrheumdis-2012-eular.3146 · 9.27 Impact Factor
  • Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):349-349. DOI:10.1136/annrheumdis-2012-eular.2572 · 9.27 Impact Factor

Publication Stats

5k Citations
663.96 Total Impact Points


  • 2004–2015
    • Copenhagen University Hospital
      København, Capital Region, Denmark
  • 2007–2014
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 2013
    • McGill University Health Centre
      • Epidemiology Clinic
      Montréal, Quebec, Canada
    • McGill University
      Montréal, Quebec, Canada
  • 2006–2013
    • Statens Serum Institut
      • • Department of Clinical Biochemistry and Immunology
      • • Department of Epidemiology Research
      Copenhagen, Capital Region, Denmark
  • 2004–2013
    • Bispebjerg Hospital, Copenhagen University
      • Department of Dermatology
      Copenhagen, Capital Region, Denmark
  • 2012
    • Glostrup Hospital
      • Department of Rheumatology
      Glostrup, Capital Region, Denmark
  • 2004–2012
    • Rigshospitalet
      • Department of Rheumatology
      Copenhagen, Capital Region, Denmark
  • 2010–2011
    • Odense University Hospital
      Odense, South Denmark, Denmark
    • University of Southern Denmark
      • Institute of Regional Health Research
      Odense, South Denmark, Denmark
  • 1992–2010
    • Copenhagen University Hospital Hvidovre
      • • Department of Radiology
      • • Department of Clinical Biochemistry
      • • Danish Research Centre for Magnetic Resonance
      Hvidovre, Capital Region, Denmark
  • 2008–2009
    • National University (California)
      San Diego, California, United States
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain
  • 1989–1997
    • Frederiksberg Hospital
      Фредериксберг, Capital Region, Denmark