Marten Trendelenburg

Universitätsspital Basel, Bâle, Basel-City, Switzerland

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Publications (77)279.21 Total impact

  • 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.
    Clinical Immunology 07/2015; 160(2). DOI:10.1016/j.clim.2015.06.014 · 3.67 Impact Factor
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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
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):568.2-568. DOI:10.1136/annrheumdis-2015-eular.2577 · 10.38 Impact Factor
  • 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.
    Molecular Immunology 04/2015; 67(1). DOI:10.1016/j.molimm.2015.03.007 · 2.97 Impact Factor
  • 25th International Complement Workshop; 10/2014
  • 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.
    Lupus 09/2014; 24(1). DOI:10.1177/0961203314550223 · 2.20 Impact Factor
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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.
    Journal of Neuroimmunology 09/2014; 274(1-2). DOI:10.1016/j.jneuroim.2014.07.001 · 2.47 Impact Factor
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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.
    Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology 08/2014; 144:w13990. DOI:10.4414/smw.2014.13990 · 2.09 Impact Factor
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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.
    12/2013; 2013:962695. DOI:10.1155/2013/962695
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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.
    PLoS ONE 12/2013; 8(12):e81755. DOI:10.1371/journal.pone.0081755 · 3.23 Impact Factor
  • S. Thanei · D. Vanhecke · C. Ploix · M. Trendelenburg
    Molecular Immunology 12/2013; 56(3):278-279. DOI:10.1016/j.molimm.2013.05.113 · 2.97 Impact Factor
  • 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.
    Molecular Immunology 12/2013; 56(3):274. DOI:10.1016/j.molimm.2013.05.102 · 2.97 Impact Factor
  • Molecular Immunology 12/2013; 56(3):251-252. DOI:10.1016/j.molimm.2013.05.039 · 2.97 Impact Factor
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    Paula Scharein · Marten Trendelenburg
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    ABSTRACT: Reducing medical errors has become an international concern. Population-based studies consistently demonstrate inacceptable high rates of medical injury and preventable deaths. Thus, electronic critical incident reporting systems are now increasingly used in hospitals, predominantly in anesthesia. However, studies systematically analyzing critical incidents are scarce. Our aim was to describe content and causes of critical incidents in our Clinic for Internal Medicine. We retrospectively analyzed all critical incidents reported during a 54-months period. Between implementation and analysis, 456 incidents were reported anonymously in the commercially available platform-independent, web-based critical incident reporting system. All incidents were analyzed according to the reporting profession, time point during hospitalization process, content and potential causes.Most incidents occurred on medical wards (80%). The most frequent type of incidents was medication errors (62%). These incidents primarily occurred when prescribing and/or administering drugs (30% and 29% of medication errors respectively). So-called [single low-9 quotation mark]human errors', i.e. occurring without apparent external factor, were the most frequently indicated cause of critical incidents (56%) followed by insufficient communication (26%). These problems primarily occurred between different groups of health care professionals and between different departments. The described types and reasons of critical incidents remained stable during the observation period. The findings of our analysis of the character and type of critical incidents occurring in a tertiary care clinic for internal medicine reported in an anonymous, voluntary, electronic reporting system suggest that strategies to improve communication and medication delivery are most promising to avoid critical incidents.
    BMC Research Notes 07/2013; 6(1):276. DOI:10.1186/1756-0500-6-276
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    ABSTRACT: Background In HIV-infected patients, prediction of Cytomegalovirus (CMV) disease remains difficult. A protective role of mannan-binding lectin (MBL) and ficolins against CMV disease has been reported after transplantation, but the impact in HIV-infected patients is unclear. Methods In a case-control study nested within the Swiss HIV Cohort Study, we investigated associations between plasma levels of MBL/ficolins and CMV disease. We compared HIV-infected patients with CMV disease (cases) to CMV-seropositive patients without CMV disease (controls) matched for CD4 T-cells, sampling time, and use of combination antiretroviral therapy. MBL and M-ficolin, L-ficolin, and H-ficolin were quantified using ELISA. Results We analysed 105 cases and 105 matched controls. CMV disease was neither associated with MBL (odds ratio [OR] 1.03 per log10 ng/mL increase (95% CI 0.73–1.45)) nor with ficolins (OR per log10 ng/mL increase 0.66 (95% CI 0.28–1.52), 2.34 (95% CI 0.44–12.36), and 0.89 (95% CI 0.26–3.03) for M-ficolin, L-ficolin, and H-ficolin, respectively). We found no evidence of a greater association between MBL and CMV disease in patients with low CD4 counts; however in the multivariable analysis, CMV disease was more likely in patients with an increased HIV RNA (OR 1.53 per log10 copies/mL; 95% CI 1.08–2.16), or a shorter duration of HIV-infection (OR 0.91 per year; 95% CI 0.84–0.98). Conclusions CMV disease is not associated with low levels of MBL/ficolins, suggesting a lack of a protective role in HIV-infected patients.
    PLoS ONE 01/2013; 8(1):e51983. DOI:10.1371/journal.pone.0051983 · 3.23 Impact Factor
  • Dominique Vanhecke · Marten Trendelenburg
    Immunobiology 11/2012; 217(11):1176. DOI:10.1016/j.imbio.2012.08.136 · 3.04 Impact Factor
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    ABSTRACT: Objective: Autoantibodies against C1q strongly correlate with the occurrence of severe nephritis in patients with systemic lupus erythematosus (SLE). We undertook this study to determine whether identification of the C1q epitope(s) recognized by these autoantibodies might lead to a better diagnostic assay and help elucidate the putative role of C1q and anti-C1q in SLE. Methods: SLE patient-derived anti-C1q Fab were used in a microarray-based peptide scan to identify the peptide sequence recognized by anti-C1q. Anti-C1q Fab binding to the target peptide was further analyzed using real-time interaction measurements (surface plasmon resonance) and peptide-based enzyme-linked immunosorbent assays (ELISAs). Results: A peptide scan of the collagen-like region of C1q identified 2 regions, 1 on the A chain and 1 on the B chain, that were the targets of the anti-C1q Fab. Binding was confirmed by surface plasmon resonance and showed nanomolar affinity. The A chain-derived peptide could specifically be detected in a peptide-based ELISA by SLE patient sera. Competition experiments suggested that this peptide represented one of the major linear epitopes of C1q that is the target of anti-C1q in SLE. Serum antibodies from most SLE patients but not from healthy individuals specifically bound to this epitope. Binding to the peptide correlated with binding of the same sera to native C1q but was found to be more sensitive for the detection of lupus nephritis. Conclusion: We identified a major linear epitope of C1q that is the target of anti-C1q in SLE. The ELISA using this peptide was more specific and more sensitive than a conventional anti-C1q assay for the detection of active nephritis in SLE patients.
    Arthritis & Rheumatology 11/2012; 64(11). DOI:10.1002/art.34605 · 7.76 Impact Factor
  • Immunobiology 11/2012; 217(11):1184-1185. DOI:10.1016/j.imbio.2012.08.160 · 3.04 Impact Factor
  • Immunobiology 11/2012; 217(11):1202. DOI:10.1016/j.imbio.2012.08.210 · 3.04 Impact Factor
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    ABSTRACT: Local renal ischemia is regarded as an important factor in the development of contrast-induced nephropathy (CIN). Mannose-binding lectin (MBL) is involved in the tissue damage during experimental ischemia/reperfusion injury of the kidneys. The aim of the present study was to investigate the association of MBL deficiency with radiocontrast-induced renal dysfunction in a large prospective cohort. 246 patients with advanced non-dialysis-dependent renal dysfunction who underwent radiographic contrast procedures were included in the study. Baseline serum MBL levels were analyzed according to the occurrence of a creatinine-based (increase of ≥0.5 mg/dL or ≥25% within 48 hours) or cystatin C-based (increase of ≥10% within 24 hours) CIN. The incidence of creatinine-based and cystatin C-based CIN was 6.5% and 24%, respectively. MBL levels were not associated with the occurrence of creatinine-based CIN. However, patients that experienced a cystatin C increase of ≥10% showed significantly higher MBL levels than patients with a rise of <10% (median 2885 (IQR 1193-4471) vs. 1997 (IQR 439-3504)ng/mL, p = 0.01). In logistic regression analysis MBL deficiency (MBL levels≤500 ng/ml) was identified as an inverse predictor of a cystatin C increase ≥10% (OR 0.34, 95% CI 0.15-0.8, p = 0.01). MBL deficiency was associated with a reduced radiocontrast-induced renal dysfunction as reflected by the course of cystatin C. Our findings support a possible role of MBL in the pathogenesis of CIN.
    BMC Nephrology 09/2012; 13(1):99. DOI:10.1186/1471-2369-13-99 · 1.69 Impact Factor

Publication Stats

852 Citations
279.21 Total Impact Points


  • 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
  • 2009
    • University of Geneva
      • Department of Rehabilitation and Geriatrics
      Genève, GE, Switzerland
  • 2004
    • Imperial College London
      • Faculty of Medicine
      Londinium, England, United Kingdom
  • 2003
    • Ealing, Hammersmith & West London College
      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