Tom Eirik Mollnes

Norwegian University of Science and Technology, Nidaros, Sør-Trøndelag, Norway

Are you Tom Eirik Mollnes?

Claim your profile

Publications (206)771.12 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic fatigue syndrome (CFS) is a prevalent and disabling condition among adolescents. The pathophysiology is poorly understood, but low-grade systemic inflammation has been suggested as an important component. This study compared circulating levels of individual cytokines and parameters of cytokine networks in a large set of adolescent CFS patients and healthy controls, and explored associations between cytokines and symptoms in the CFS group. CFS patients (12-18 years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project (ClinicalTrials ID: NCT01040429). A broad case definition of CFS was applied, requiring three months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Thus, the case definition was broader than the Fukuda-criteria of CFS. Healthy controls having comparable distribution of gender and age were recruited from local schools. Twenty-seven plasma cytokines, including interleukins, chemokines and growth factors were assayed using multiplex technology. The results were subjected to network analyses using the ARACNE algorithm. Symptoms were charted by a questionnaire, and patients were subgrouped according to the Fukuda-criteria. A total of 120 CFS patients and 68 healthy controls were included. CFS patients had higher scores for fatigue (p<0.001) and inflammatory symptoms (p<0.001) than healthy controls. All cytokine levels and cytokine network parameters were similar, and none of the differences were statistically different across the two groups, also when adjusting for adherence to the Fukuda criteria of CFS. Within the CFS group, there were no associations between aggregate cytokine network parameters and symptom scores. Adolescent CFS patients are burdened by symptoms that might suggest low-grade systemic inflammation, but plasma levels of individual cytokines as well as cytokine network measures were not different from healthy controls, and there were no associations between symptoms and cytokine expression in the CFS group. Low-grade systemic inflammation does not appear to be a central part of adolescent CFS pathophysiology. Copyright © 2014. Published by Elsevier Inc.
    Brain Behavior and Immunity 12/2014; · 5.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with genetically determined deficiency of complement component 5 are usually diagnosed because of recurrent invasive Neisseria meningitidis infections. Approximately 40 individual cases have been diagnosed worldwide. Nevertheless, reports of the responsible genetic defects have been sporadic, and we know of no previous reports of C5 deficiency being associated with a number of independent meningococcal disease cases in particular communities. Here we describe C5 deficiency in seven unrelated Western Cape, South African families.
    Molecular Immunology 12/2014; 46. · 3.00 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Eculizumab is a humanized IgG2/4 chimeric anti-complement C5 antibody used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) or atypical hemolytic uremic syndrome. The aim of this study was to evaluate whether or not the complement activity in newborns from pregnant women who receive eculizumab is impaired. A novel eculizumab-C5 complex (E-C5) specific assay was developed and revealed that two newborns carried only 6–7% of the E-C5 detected in their eculizumab-treated PNH mothers. Serum from the pregnant women completely lacked terminal complement pathway activity, whereas the complement activity in the serum of the newborns was completely normal. Data from the pregnant women and their newborns were compared with that of healthy age-matched female controls and healthy newborns, as well as a non-treated pregnant woman with PNH and her newborn. These all showed normal complement activity without detectable E-C5 complexes. Furthermore, absence of eculizumab or E-C5 in the newborn could not be explained by lack of eculizumab binding to the neonatal Fc receptor (FcRn), as eculizumab bound strongly to the receptor in vitro. In conclusion, despite binding to FcRn neither eculizumab nor E-C5 accumulates in fetal plasma, and eculizumab treatment during pregnancy does not impair the complement function in the newborn.
    Immunobiology 11/2014; · 2.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionWhole-body ischemia and reperfusion trigger a systemic inflammatory response. This study analyzed the effect of temperature on the inflammatory response in patients treated with prolonged mild hypothermia after cardiac arrest.Methods Ten comatose patients with return of spontaneous circulation (ROSC) after pulseless electrical activity (PEA)/asystole or prolonged ventricular fibrillation were treated with mild therapeutic hypothermia for 72 hours after admission to a tertiary care university hospital. On admission and at 12, 24, 36, 48, 72, 96 and 114 h temperature was measured and blood samples were taken from the arterial catheter. Proinflammatory interleukin (IL)-6 and anti-inflammatory (IL-10) cytokines and chemokines (IL-8 and monocyte chemotactic protein1 (MCP-1)), the intercellular adhesion molecule 1 (ICAM-1), and complement activation products (C1rs-C1-INH, C4bc, C3bPBb, C3bc and TCC) were measured. Changes over time were analyzed with the repeated measures test for non-parametric data. The Dunn's Multiple Comparison Test was used for comparison of individual time points.ResultsMedian temperature at the start of the study was 34.3°C (33.4 to 35.2) and was maintained between 32 to 34°C for 72 h. All patients were passively rewarmed after 72 h from 33.7°C (33.1 to 33.9) at 72 h to 38.0°C (37.5 to 38.1) at 114 h after admission (P <0.001). In general, the cytokines and chemokines remained stable during hypothermia and decreased during rewarming, whereas complement activation was suppressed during the whole hypothermia period and increased modestly during rewarming.Conclusions Prolonged hypothermia possibly blunts the inflammatory response after rewarming in patients after cardiac arrest. Complement activation was low during the whole hypothermia period, indicating that complement activation is highly temperature sensitive also in vivo. Since inflammation is a strong mediator of secondary brain injury, a blunted pro-inflammatory response after rewarming may be beneficial.
    Critical care (London, England) 10/2014; 18(5):546. · 5.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-γ, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard.
    Biomaterials 10/2014; · 8.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Heart diseases are common and significant contributors to worldwide mortality and morbidity. During recent years complement mediated inflammation has been shown to be an important player in a variety of heart diseases. Despite some negative results from clinical trials using complement inhibitors, emerging evidence points to an association between the complement system and heart diseases. Thus, complement seems to be important in coronary heart disease as well as in heart failure, where several studies underscore the prognostic importance of complement activation. Furthermore, patients with atrial fibrillation often share risk factors both with coronary heart disease and heart failure, and there is some evidence implicating complement activation in atrial fibrillation. Moreover, Chagas heart disease, a protozoal infection, is an important cause of heart failure in Latin America, and the complement system is crucial for the protozoa–host interaction. Thus, complement activation appears to be involved in the pathophysiology of a diverse range of cardiac conditions. Determination of the exact role of complement in the various heart diseases will hopefully help to identify patients that might benefit from therapeutic complement intervention.
    Molecular Immunology 10/2014; · 3.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cholesterol crystals are known to be a hallmark of atherosclerosis with recent studies demonstrating deposition of these crystals in early fatty streak formation as well as penetrating the intima following plaque rupture. Inflammation has also become a central focus in atheroma development and endothelial cell activation is recognized as necessary for the recruitment of inflammatory cells to the plaque. However, the extent to which cholesterol crystals can induce inflammation and activate endothelial cells is not known. To investigate this, we developed a novel model activating human umbilical vein endothelial cells using lepirudin anticoagulated human whole blood. We found that cholesterol crystals caused a marked and dose-dependent increase in the adhesion molecules E-selectin and ICAM-1 on the surface of the endothelial cells after incubation with whole blood. There was no activation of the cells when the crystals were incubated in medium alone, or in human serum, despite substantial crystal-induced complement activation in serum. Complement inhibitors at the C3 and C5 levels reduced the whole blood induced endothelial cell activation by up to 89% (p < 0.05) and abolished TNF release (p < 0.01). Finally, the TNF inhibitor infliximab reduced endothelial activation to background levels (p < 0.05). In conclusion, these data demonstrate that endothelial activation by cholesterol crystals is mediated by complement-dependent TNF release, and suggests that complement-inhibition might have a role in alleviating atherosclerosis-induced inflammation.
    Immunobiology 10/2014; · 2.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies have shown that activation of the complement system may be associated with long-term graft function. The aim of this retrospective study was to assess the impact of the pattern recognition molecules of the lectin pathway on long-term graft survival after kidney transplantation.
    Transplantation 09/2014; · 3.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The complement system can be activated via the lectin pathway by the recognition molecules mannose-binding lectin (MBL) and the ficolins. Ficolin-2 exhibits binding against a broad range of ligands including biomaterials in vitro and low Ficolin-2 levels are associated with increased risk of infections. Thus, we investigated the biocompatibility of the recognition molecules of the lectin pathway in two different types of cardiopulmonary bypass circuits.Blood were drawn at five time points before, during and post-operatively from 30 patients undergoing elective cardiac surgery. Patients were randomized in two groups using different coatings of cardiopulmonary bypass circuits, Phisio® (phosporylcholine polymer coating) and Bioline® (albumin-heparin coating). Concentrations of MBL, Ficolin-1, -2 and -3 and soluble C3a and terminal complement complex (TCC) in plasma samples were measured. Ficolin-3 mediated complement activation potential was evaluated with C4, C3 and TCC as output.There was no significant difference between the two circuit materials regarding MBL, Ficolin-1 and -3. In the Bioline® group the Ficolin-2 levels significantly decreased after initiation of surgery (P<0.0001) and remained reduced throughout the sampling period. This was not seen for Phisio® coated circuits. Ficolin-3 mediated complement activation potential was significantly reduced in both groups after start of operation (P<0.0001), whereas soluble C3a and TCC in the samples were increased (P<0.0001).Ficolin-2 was depleted from plasma during cardiac surgery when using heparin coated bypass circuits and did not reach base line level 24 hours post-operation. These findings may have implications for the postoperative susceptibility to infections in patients undergoing extracorporeal circulation procedures.
    Clinical & Experimental Immunology 09/2014; · 3.28 Impact Factor
  • Source
    Molecular Immunology 08/2014; 60(2):115. · 3.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: As major depression (MD) is often comorbid with alcohol-use disorders (AUD) and alcohol itself modulates the immune system, we examined serum levels of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF), and interferon (IFN)-γ in AUD patients with and without MD. Putative interactions between alcohol variables and MD on cytokine levels were also assessed.
    CNS Neuroscience & Therapeutics 07/2014; · 3.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Atypical hemolytic uremic syndrome (aHUS) is associated with (genetic) alterations in alternative complement pathway. Nevertheless, comprehensive evidence that the complement system in aHUS patients is more prone to activation is still lacking. Therefore, we performed a thorough analysis of complement activation in acute phase and in remission of this disease.Complement activation patterns of the aHUS patients in acute phase and in remission were compared to those of healthy controls. Background levels of complement activation products C3b/c, C3bBbP and TCC were measured using ELISA in EDTA plasma. In vitro triggered complement activation in serum samples was studied using zymosan-coating and pathway-specific assay. Furthermore, efficiencies of the C3b/c, C3bBbP and TCC generation in fluid phase during spontaneous activation were analyzed.Patients with acute aHUS showed elevated levels of C3b/c (P<0.01), C3bBbP (P<0.0001) and TCC (P<0.0001) in EDTA plasma, while values of patients in remission were normal, compared to those of healthy controls. Using data from a single aHUS patient with complement factor B mutation we illustrated normalization of complement activation during aHUS recovery. Serum samples from patients in remission showed normal in vitro patterns of complement activation and demonstrated normal kinetics of complement activation in the fluid phase.Our data indicate that while aHUS patients have clearly activated complement in acute phase of the disease, this is not the case in remission of aHUS. This knowledge gives important insight into complement regulation in aHUS and may have an impact on monitoring of these patients, particularly when using complement inhibition therapy.
    Clinical & Experimental Immunology 07/2014; · 3.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Complement convertases are enzymatic complexes that play a central role in sustaining and amplification of the complement cascade. Impairment of complement function directly or indirectly leads to pathologic conditions including higher infection rate, kidney diseases, autoimmune- or neurodegenerative diseases and ischemia-reperfusion injury. An assay for direct measurement of activity of the convertases in patient sera is not available. Existing assays testing convertase function are based on purified complement components and thus, convertase formation occurs under non-physiological conditions. We designed a new assay, in which C5 blocking compounds enabled separation of the complement cascade into two phases: the first ending at the stage of C5 convertases and the second ending with membrane attack complex formation. Use of rabbit erythrocytes or antibody-sensitized sheep erythrocytes as the platforms for convertase formation enabled easy readout based on measurement of hemolysis. Thus, properties of patient sera could be studied directly regarding convertase activity and membrane attack complex formation. Another advantage of this assay was the possibility to screen for host factors such as C3 nephritic factor and other anti-complement autoantibodies, or gain-of-function mutations, which prolong half-live of complement convertases. Herein, we present proof of concept, detailed description and validation of this novel assay.
    Clinical & Experimental Immunology 05/2014; · 3.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sepsis and septic shock, caused by an excessive systemic host-inflammatory response, are associated with high morbidity and mortality. The complement system and TLRs provide important pattern recognition receptors initiating the cytokine storm by extensive cross-talk. We hypothesized that double blockade of complement C5 and the TLR coreceptor CD14 could improve survival of experimental polymicrobial sepsis. Mice undergoing cecal ligation and puncture (CLP)-induced sepsis were treated with neutralizing anti-CD14 Ab biG 53, complement C5 inhibitor coversin (Ornithodoros moubata C inhibitor), or a combination thereof. The inflammatory study (24-h observation) revealed statistically significant increases in 22 of 24 measured plasma biomarkers in the untreated CLP group, comprising 14 pro- and anti-inflammatory cytokines and 8 chemokines, growth factors, and granulocyte activation markers. Single CD14 or C5 blockade significantly inhibited 20 and 19 of the 22 biomarkers, respectively. Combined CD14 and C5 inhibition significantly reduced all 22 biomarkers (mean reduction 85%; range 54-95%) compared with the untreated CLP group. Double blockade was more potent than single treatment and was required to significantly inhibit IL-6 and CXCL1. Combined inhibition significantly reduced morbidity (motility and eyelid movement) and mortality measured over 10 d. In the positive control CLP group, median survival was 36 h (range 24-48 h). Combined treatment increased median survival to 96 h (range 24-240 h) (p = 0.001), whereas survival in the single-treatment groups was not significantly increased (median and range for anti-CD14 and anti-C5 treatment were 36 h [24-48 h] and 48 h [24-96 h]). Combined with standard intervention therapy, specific blockade of CD14 and C5 might represent a promising new therapeutic strategy for treatment of polymicrobial sepsis.
    The Journal of Immunology 04/2014; · 5.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies link Toll-like receptor 3 (TLR3) to the pathogenesis of inflammatory bowel disease (IBD). Screening TLR3-agonist response in an intestinal epithelial cell line, we found complement factor B mRNA (CFB) potently upregulated and went on to further study localization of complement factor B synthesis and systemic activation of complement in ulcerative colitis and Crohn's disease. In a transcriptome analysis of poly (I:C) stimulated HT-29 cells, we found CFB highly upregulated downstream of TLR3. We sought to confirm CFB upregulation in a microarray gene expression analysis on colonic biopsies from an IBD population (n = 133). Immunohistochemical staining and in situ hybridization were done to identify cellular sources of factor B and CFB. Systemic complement activation was assessed in plasma (n = 18) using neoepitope-based enzyme linked immunosorbent assay. CFB mRNA and protein were abundantly expressed in the colonic epithelial cell line, and synthesis enhanced by the poly (I:C) TLR3 ligand. In inflamed versus normal colonic mucosa of ulcerative colitis and Crohn's disease, CFB mRNA was the most significantly overexpressed gene and the mRNA abundance ratio was among the 50 highest. Epithelial cells were the dominating site of factor B expression. Systemic complement activation was significantly higher in active than in nonactive IBD. This study is the first to link TLR3 to activation of the alternative complement pathway. Complement factor B is potently upregulated locally in IBD in addition to having a possible central role in systemic complement activation. This suggests a prominent role for complement in IBD pathogenesis.
    Inflammatory Bowel Diseases 04/2014; · 5.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Inflammation is associated with development of atherosclerosis, and cholesterol crystals (CC) have long been recognized as a hallmark of atherosclerotic lesions. CC appear early in the atheroma development and trigger inflammation by NLRP3 inflammasome activation. In this study we hypothesized whether CC employ the complement system to activate inflammasome/caspase-1, leading to release of mature IL-1β, and whether complement activation regulates CC-induced cytokine production. In this study we describe that CC activated both the classical and alternative complement pathways, and C1q was found to be crucial for the activation. CC employed C5a in the release of a number of cytokines in whole blood, including IL-1β and TNF. CC induced minimal amounts of cytokines in C5-deficient whole blood, until reconstituted with C5. Furthermore, C5a and TNF in combination acted as a potent primer for CC-induced IL-1β release by increasing IL-1β transcripts. CC-induced complement activation resulted in upregulation of complement receptor 3 (CD11b/CD18), leading to phagocytosis of CC. Also, CC mounted a complement-dependent production of reactive oxygen species and active caspase-1. We conclude that CC employ the complement system to induce cytokines and activate the inflammasome/caspase-1 by regulating several cellular responses in human monocytes. In light of this, complement inhibition might be an interesting therapeutic approach for treatment of atherosclerosis.
    The Journal of Immunology 02/2014; · 5.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Co-infection with malaria and HIV increases the severity and mortality of both diseases, but the cytokine responses related to this co-infection are only partially characterised. The aim of this study was to explore cytokine responses in relation to severity and mortality in malaria patients with and without HIV co-infection. This was a prospective cross-sectional study. Clinical data and blood samples were collected from adults in Mozambique. Plasma was analysed for 21 classical pro- and anti-inflammatory cytokines, including interleukins, interferons, and chemokines. We included 212 in-patients with fever and/or suspected malaria and 56 healthy controls. Falciparum malaria was diagnosed in 131 patients, of whom 70 were co-infected with HIV-1. The malaria patients had marked increases in their cytokine responses compared with the healthy controls. Some of these changes, particularly interleukin 8 (IL-8) and interferon-γ-inducing protein 10 (IP-10) were strongly associated with falciparum malaria and disease severity. Both these chemokines were markedly increased in patients with falciparum malaria as compared with healthy controls, and raised levels of IL-8 and IP-10 were associated with increased disease severity, even after adjusting for relevant confounders. For IL-8, particularly high levels were found in malaria patients that were co-infected with HIV and in those who died during hospitalization. Our findings underscore the complex role of inflammation during infection with P. falciparum, and suggest a potential pathogenic role for IL-8 and IP-10. However, the correlations do not necessarily mean any causal relationship, and further both clinical and mechanistic research is necessary to elucidate the role of cytokines in pathogenesis and protection during falciparum malaria.
    PLoS ONE 01/2014; 9(12):e114480. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Meconium displaces surfactant from the alveolar surface and inhibits its function. The development of active synthetic surfactants is complicated, especially to synthesize the hydrophobic surfactant proteins SP-B and SP-C. A synthetic surfactant, CHF5633 containing SP-B and SP-C analogs, has been designed to act similarly to the natural surfactant poractant alfa. Objective: To test the resistance to meconium inactivation of CHF5633 compared to poractant alfa. Secondary outcome measurements were respiratory and inflammatory parameters. Methods: Twenty-six newborn pigs, bodyweight 1.4-2.0 kg were randomized to receive either poractant alfa or CHF5633. After anesthesia, surgery and final stabilization, meconium was instilled endotracheally followed by surfactant. Bronchial lavage fluid was obtained before intervention and every second hour. Respiratory parameters were registered and blood samples drawn before intervention and every hour. Results: Surfactant was inactivated in both groups 6 h after meconium instillation, but CHF5633 was more resistant than poractant alfa in terms of lipid peroxidation. Respiratory parameters were similar in both groups. Inflammatory and hemostatic parameters differed between groups, suggesting that the surfactants may play different roles in the meconium-induced inflammatory process. Due to the differential effects and complex pattern observed, the data do not indicate that one of the surfactants was superior with respect to inflammatory and hemostatic responses. Conclusion: This study indicates that CHF5633 is as efficient as poractant alfa in experimental meconium aspiration syndrome. © 2013 S. Karger AG, Basel.
    Neonatology 12/2013; 105(2):128-135. · 2.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There is increasing evidence that complement may play a role in bone development. Our previous studies demonstrated that the key complement receptor C5aR was strongly expressed in the fracture callus not only by immune cells but also by bone cells and chondroblasts, indicating a function in bone repair. To further elucidate the role of complement in bone healing, this study investigated fracture healing in mice in the absence of the key complement molecules C3 and C5. C3(-/-) and C5(-/-) as well as the corresponding wildtype mice received a standardized femur osteotomy, which was stabilized using an external fixator. Fracture healing was investigated after 7 and 21 days using histological, micro-computed tomography and biomechanical measurements. In the early phase of fracture healing, reduced callus area (C3(-/-): -25%, p=0.02; C5(-/-): -20% p=0.052) and newly formed bone (C3(-/-): -38%, p=0.01; C5(-/-): -52%, p=0.009) was found in both C3- and C5-deficient mice. After 21 days, healing was successful in the absence of C3, whereas in C5-deficient mice fracture repair was significantly reduced, which was confirmed by a reduced bending stiffness (-45%; p=0.029) and a smaller callus volume (-17%; p=0.039). We further demonstrated that C5a was activated in C3(-/-) mice, suggesting cleavage via extrinsic pathways. Our results suggest that the activation of the terminal complement cascade in particular may be crucial for successful fracture healing.
    PLoS ONE 11/2013; 8(11):e81341. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate biomarker patterns in rheumatoid arthritis (RA) with extraarticular manifestations. Cartilage oligomeric matrix protein (COMP), COMP-C3b, and soluble terminal complement complexes (sTCC) were measured by ELISA. COMP-C3b levels were higher in patients with RA than in healthy controls and lower in extraarticular RA (ExRA) than in RA controls. In patients with ExRA, sTCC levels were higher than in RA controls, and correlated inversely with serum COMP-C3b levels in the ExRA group. Patients with ExRA had lower levels of COMP-C3b. This may be a consequence of complement consumption or a lower potential for COMP from these patients to activate complement.
    The Journal of Rheumatology 11/2013; · 3.17 Impact Factor

Publication Stats

3k Citations
771.12 Total Impact Points


  • 2008–2014
    • Norwegian University of Science and Technology
      • • Centre of Molecular Inflammation Research
      • • Department of Cancer Research and Molecular Medicine
      Nidaros, Sør-Trøndelag, Norway
  • 1994–2014
    • Universitetet i Tromsø
      • Department of Clinical Medicine (IKM)
      Tromsø, Troms, Norway
    • University of Oslo
      • • Department of Immunology (IMM)
      • • Research Institute for Internal Medicine (IIM)
      • • Division of Surgery
      Kristiania (historical), Oslo County, Norway
  • 2013
    • IT University of Copenhagen
      København, Capital Region, Denmark
    • Semmelweis University
      • Third Department of Internal Medicine
      Budapest, Budapest fovaros, Hungary
  • 2002–2012
    • Oslo University Hospital
      • • Division of Emergencies and Critical Care
      • • Department of Cardiothoracic Surgery
      • • Department of Medical Biochemistry
      Oslo, Oslo, Norway
  • 1994–2012
    • Nordlandssykehuset Bodoe
      Bodø, Nordland, Norway
  • 2011
    • Centre for Ecology & Hydrology
      Wallingford, England, United Kingdom
  • 2010
    • Democritus University of Thrace
      • Department of Internal Medicine II
      Komotiní, Anatoliki Makedonia kai Thraki, Greece
  • 2009–2010
    • Haukeland University Hospital
      • Department of Thoracic Medicine
      Bergen, Hordaland Fylke, Norway
    • Norwegian Institute of Public Health
      Kristiania (historical), Oslo County, Norway
    • University of Bristol
      • School of Veterinary Sciences
      Bristol, England, United Kingdom
  • 2007
    • Hospital of the University of Pennsylvania
      • Department of Pathology and Laboratory Medicine
      Philadelphia, PA, United States
  • 2003
    • Universität Heidelberg
      • Institute of Immunology and Serology
      Heidelberg, Baden-Wuerttemberg, Germany
    • Radboud University Nijmegen
      • Department of General Internal Medicine
      Nijmegen, Provincie Gelderland, Netherlands