Søren Jacobsen

Rigshospitalet, København, Capital Region, Denmark

Are you Søren Jacobsen?

Claim your profile

Publications (186)767.62 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Endothelial damage and activation may play central roles in the pathogenesis of systemic sclerosis (SSc) and are reflected by microparticles (MPs) and soluble selectins. The objective of this study was to determine if these potential biomarkers are associated with specific organ involvements or cutaneous subgroups of SSc patients. MPs in platelet-poor plasma from 121 patients with SSc, 79 and 42 with limited and diffuse cutaneous disease, respectively, were characterized by flow cytometry for their capacity to bind annexin V in combination with surface markers of either platelets (PMPs), leukocytes (LMPs) or endothelial cells (EMPs). Soluble E- and P-selectin levels were determined in plasma. By correlation analyses, this was held against involvement of skin, lung function, lung fibrosis, pulmonary artery hypertension, and serology. None of the markers were associated with cutaneous subgroups of SSc. Concentrations of annexin V non-binding EMPs and annexin V non-binding LMPs were negatively correlated to pulmonary diffusing capacity (DLCO) (r = -0.28; p = 0.003; r = -0.26; p = 0.005) and forced vital capacity (FVC) (r = -0.24; p = 0.009; r = -0.29; p = 0.002), driven by patients with limited and diffuse cutaneous disease, respectively. Soluble E-selectin levels correlated negatively to DLCO (r = -0.21, p = 0.03) and FVC (r = -0.25; p = 0.007); and soluble P-selectin correlated negatively to DLCO (r = -0.23, p = 0.01). Negative correlations between annexin V non-binding EMP and LMP concentrations with lung function parameters (DLCO and FVC) differed between limited and diffuse cutaneous subsets of SSc, indicative of various pathogeneses of lung involvement in SSc, possibly with a differential role of MPs.
    BMC Musculoskeletal Disorders 12/2015; 16(1):191. DOI:10.1186/s12891-015-0653-8 · 1.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Cardiac events are a major cause of death in patients with idiopathic inflammatory myopathies (IIM). The study objective was in a controlled setting to describe cardiac abnormalities by non-invasive methods in a cohort of patients with polymyositis (PM) or dermatomyositis (DM) and to identify predictors for cardiac dysfunction. Methods In a cross-sectional study, 76 patients with PM/DM and 48 matched healthy controls (HC) were assessed by serum levels of cardiac troponin-I (TnI), electrocardiography, Holter monitoring, echocardiography with tissue Doppler imaging (TDI) and quantitative cardiac (99m) technetium pyrophosphate ((99m) Tc-PYP) scintigraphy. Results Compared to HCs, patients with PM/DM more frequently had left ventricular diastolic dysfunction (LVDD) (12% vs. 0%, P = 0.02) and longer QRS and QTc intervals (P = 0.007 and P < 0.0001, respectively). In multivariate analysis, factors associated with LVDD were age (P = 0.001), disease duration (P = 0.004), presence of myositis specific/associated autoantibodies (P = 0.05), and high cardiac (99m) Tc-PYP uptake (P = 0.006). In multivariate analysis of the pooled data for patients and HCs, a diagnosis of PM/DM (P < 0.0001) was associated with LVDD. Conclusions Patients with PM or DM had an increased prevalence of cardiac abnormalities compared to HCs. LVDD was a common occurrence in PM/DM patients and correlated to disease duration. In addition, the association of LVDD with myositis specific/associated autoantibodies and high cardiac (99m) Tc-PYP uptake supports the notion of underlying autoimmunity and myocardial inflammation in patients with PM/DM. This article is protected by copyright. All rights reserved.
    10/2015; DOI:10.1002/acr.22772
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: In this study, we examined the concentration of serum immunoglobulin free light chains (FLCs) in systemic lupus erythematosus (SLE) patients and investigated its association with various disease parameters in order to evaluate the role of FLCs as a potential biomarker in SLE. Furthermore, FLCs' association with Epstein-Barr virus (EBV) antibodies was examined. Methods: Using a nephelometric assay, κFLC and λFLC concentrations were quantified in sera from 45 SLE patients and 40 healthy controls. SLE patients with renal insufficiency were excluded in order to preclude high concentrations of serum FLCs due to decreased clearance. Results: Serum FLC concentrations were significantly elevated in SLE patients compared to healthy controls (p<0.0001) also after adjusting for Ig levels (p<0.0001). The concentration of serum FLCs correlated with a global disease activity (SLE disease activity index (SLEDAI)) score of the SLE patients (r = 0.399, p = 0.007). Furthermore, concentrations of FLCs correlated with titers of dsDNA antibodies (r = 0.383, p = 0.009), and FLC levels and SLEDAI scores correlated in the anti-dsDNA-positive SLE patients, but not in anti-dsDNA-negative SLE patients. Total immunoglobulin (IgG and IgA) concentrations correlated with FLC concentrations and elevated FLC levels were additionally shown to associate with the inflammatory marker C-reactive protein and also with complement consumption determined by low C4 in SLE patients. Collectively, results indicated that elevated serum FLCs reflects increased B cell activity in relation to inflammation. SLE patients had an increased seropositivity of EBV-directed antibodies that did not associate with elevated FLC concentrations. An explanation for this could be that serum FLC concentrations reflect the current EBV activity (reactivation) whereas EBV-directed antibodies reflect the extent of previous infection/reactivations. Conclusion: SLE patients have elevated concentrations of serum FLCs that correlate with global disease activity scores and especially serologic markers for active disease. These findings are suggestive of circulating FLCs having potential as a new supplementary serologic biomarker in SLE.
    PLoS ONE 09/2015; 10(9):e0138753. DOI:10.1371/journal.pone.0138753 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: Knowledge of cardiac involvement in idiopathic inflammatory myopathies (IIM) is limited, especially in the early stage of disease. The objective of the present study was to perform a controlled evaluation of cardiac abnormalities in newly diagnosed, untreated patients with idiopathic inflammatory myopathies (IIM) by means of non-invasive techniques. Methods: Fourteen patients with IIM (8 polymyositis, 4 dermatomyositis, 2 cancer-associated dermatomyositis) and 14 gender- and age- matched healthy control subjects were investigated. Participant assessments included a cardiac questionnaire, cardiac troponin-I (TnI), electrocardiogram (standard 12-lead and 48-h Holter monitoring), echocardiography with tissue Doppler measures, cardiac magnetic resonance (CMR) imaging with T2 mapping and semi-quantitative 99mtechnetium pyrophosphate (99mTc-PYP) scintigraphy. Results: Dyspnoea was present in 8 (57%) of the patients compared to none of the controls (p<0.01). Median levels of TnI in patients and controls were 20 ng/L and 6 ng/L, respectively (p=0.06). QTc intervals were prolonged in the patient group (p=0.01). Two patients had systolic dysfunction, and one diastolic dysfunction. The myocardial 99mTc-PYP uptake and CMR results differed between patients and controls, albeit not with statistical significance. Overall, cardiac abnormalities were demonstrated in 9 (64%) of the patients versus 2 (14%) of the controls (p=0.02). Conclusions: Cardiac abnormalities assessed by TnI, ECG or imaging modalities were significantly more common in newly diagnosed, treatment naïve patients with IIM compared to healthy control subjects. These abnormalities, although subclinical, may indicate that myocardial involvement is common in patients and calls for larger controlled studies and further investigations of the prognostic implications of this finding.
    Clinical and experimental rheumatology 09/2015; 33(5). · 2.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort. Patients in the Systemic Lupus International Collaborating Clinics inception cohort (≤15 months of SLE diagnosis) were assessed annually for estimated glomerular filtration rate (eGFR), proteinuria and end-stage renal disease (ESRD). Health-related quality of life was measured by the Short Form (36 questions) health survey questionnaire (SF-36) subscales, mental and physical component summary scores. There were 1827 patients, 89% females, mean (s.d.) age 35.1 (13.3) years. The mean (s.d.) SLE duration at enrolment was 0.5 (0.3) years and follow-up 4.6 (3.4) years. LN occurred in 700 (38.3%) patients: 566/700 (80.9%) at enrolment and 134/700 (19.1%) during follow-up. Patients with nephritis were younger, more frequently men and of African, Asian and Hispanic race/ethnicity. The estimated overall 10-year incidence of ESRD was 4.3% (95% CI: 2.8%, 5.8%), and with nephritis was 10.1% (95% CI: 6.6%, 13.6%). Patients with nephritis had a higher risk of death (HR = 2.98, 95% CI: 1.48, 5.99; P = 0.002) and those with eGFR <30 ml/min at diagnosis had lower SF-36 physical component summary scores (P < 0.01) and lower Physical function, Physical role and Bodily pain scores. Over time, patients with abnormal eGFR and proteinuria had lower SF-36 mental component summary (P ≤ 0.02) scores compared to patients with normal values. LN occurred in 38.3% of SLE patients, frequently as the initial presentation, in a large multi-ethnic inception cohort. Despite current standard of care, nephritis was associated with ESRD and death, and renal insufficiency was linked to lower health-related quality of life. Further advances are required for the optimal treatment of LN. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Rheumatology (Oxford, England) 09/2015; DOI:10.1093/rheumatology/kev311 · 4.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In order to study the humoral immune response against Epstein-Barr virus (EBV) in patients with rheumatoid arthritis (RA) and to compare it with the two major autoantibody types in RA, plasma samples from 77 RA patients, 28 patients with systemic lupus erythematosus (SLE), and 28 healthy controls (HCs) were investigated by enzyme-linked immunosorbent assays (ELISA). Increased percentages of positives and concentrations of IgG/IgA/IgM antibodies against the latent EBV nuclear antigen-1 (EBNA-1) were observed in RA patients compared to SLE patients and HCs. Increased concentrations and percentages of positives of IgG/IgA/IgM against the early lytic EBV antigen diffuse (EAD) were also found in RA patients compared to HCs but were highest in SLE patients. Furthermore, associations between the elevated EBNA-1 IgA and EBNA-1 IgM levels and the presence of IgM and IgA rheumatoid factors (RFs) and anti-citrullinated protein antibodies (ACPAs, IgG) and between elevated IgA concentrations against EAD and the presence of RFs and ACPAs in RA patients were found. Thus, RA patients had elevated antibodies of all isotypes characteristic of latent EBV infection (whereas SLE patients had elevated antibodies characteristic of lytic EBV infection). Notably, for IgM and IgA (but not IgG), these were associated with the presence of characteristic RA autoantibodies.
    05/2015; 2015:1-9. DOI:10.1155/2015/472174
  • [Show abstract] [Hide abstract]
    ABSTRACT: A high level of galectin-3-binding protein (G3BP) appears to distinguish circulating cell-derived microparticles in systemic lupus erythematosus (SLE). The aim of this study is to characterize the population of G3BP-positive microparticles from SLE patients compared to healthy controls, explore putative clinical correlates, and examine if G3BP is present in immune complex deposits in kidney biopsies from patients with lupus nephritis. Numbers of annexin V-binding and G3BP-exposing plasma microparticles from 56 SLE patients and 36 healthy controls were determined by flow cytometry. Quantitation of microparticle-associated G3BP, C1q and immunoglobulins was obtained by liquid chromatography tandem mass spectrometry (LC-MS/MS). Correlations between microparticle-G3BP data and clinical parameters were analyzed. Co-localization of G3BP with in vivo-bound IgG was examined in kidney biopsies from one non-SLE control and from patients with class IV (n = 2) and class V (n = 1) lupus nephritis using co-localization immune electron microscopy. Microparticle-G3BP, microparticle-C1q and microparticle-immunoglobulins were significantly (P < 0.01) increased in SLE patients by LC-MS/MS. Three G3BP-exposing microparticle populations could be discerned by flow cytometry, including two subpopulations that were significantly increased in SLE samples (P = 0.01 and P = 0.0002, respectively). No associations of G3BP-positive microparticles with clinical manifestations or disease activity were found. Immune electron microscopy showed co-localization of G3BP with in vivo-bound IgG in glomerular electron dense immune complex deposits in all lupus nephritis biopsies. Both circulating microparticle-G3BP numbers as well as G3BP expression are increased in SLE patients corroborating G3BP being a feature of SLE microparticles. By demonstrating G3BP co-localized with deposited immune complexes in lupus nephritis, the study supports cell-derived microparticles as a major autoantigen source and provides a new understanding of the origin of immune complexes occurring in lupus nephritis. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
    Lupus 04/2015; 24(11). DOI:10.1177/0961203315580146 · 2.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. With the growing use of the ESSDAI, some domains appear to be more challenging to rate than others. The ESSDAI is now in use as a gold standard to measure disease activity in clinical studies, and as an outcome measure, even a primary outcome measure, in current randomised clinical trials. Therefore, ensuring an accurate and reproducible rating of each domain, by providing a more detailed definition of each domain, has emerged as an urgent need. The purpose of the present article is to provide a user guide for the ESSDAI. This guide provides definitions and precisions on the rating of each domain. It also includes some minor improvement of the score to integrate advance in knowledge of disease manifestations. This user guide may help clinicians to use the ESSDAI, and increase the reliability of rating and consequently of the ability to detect true changes over time. This better appraisal of ESSDAI items, along with the recent definition of disease activity levels and minimal clinically important change, will improve the assessment of patients with primary SS and facilitate the demonstration of effectiveness of treatment for patients with primary SS.
    02/2015; 1(1):e000022-e000022. DOI:10.1136/rmdopen-2014-000022
  • Source
    N. S. Rasmussen · AH Draborg · C. T. Nielsen · S Jacobsen · G Houen ·
    [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 · 2.53 Impact Factor
  • L Dreyer · S Jacobsen · L Juul · L Terslev ·
    [Show abstract] [Hide abstract]
    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; 24(7). DOI:10.1177/0961203314561666 · 2.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To evaluate the expression profile of cell-free circulating microRNA (miRNA) in systemic sclerosis (SSc), healthy controls (HC), and systemic lupus erythematosus (SLE). Methods: Total RNA was purified from plasma and 45 different, mature miRNA were measured using quantitative PCR assays after reverse transcription. Samples (n = 189) were from patients with SSc (n = 120), SLE (n = 29), and from HC (n = 40). Expression data were clustered by principal components analysis, and diagnostically specific miRNA profiles were developed by leave-one-out cross-validation. Diagnostic probability scores were derived from stepwise logistic regression. Results: Thirty-seven miRNA specificities were consistently detected and 26 of these were unaffected by SSc sample age and present in more than two-thirds of SSc samples. SSc cases showed a distinct expression profile with 14/26 miRNA significantly decreased (false discovery rate < 0.05) and 5/26 increased compared with HC. A 21-miRNA classifier gave optimum accuracy (80%) for discriminating SSc from both HC and SLE. The discrimination between HC and SSc (95% accuracy) was strongly driven by miRNA of the 17 ∼ 92 cluster and by miR-16, -223, and -638, while SLE and SSc differed mainly in the expression of miR-142-3p, -150, -223, and -638. Except for a weak correlation between anti-Scl-70 and miR-638 (p = 0.048), there were no correlations with other patient variables. Conclusion: Circulating miRNA profiles are characteristic for SSc compared with both HC and SLE cases. Some of the predicted targets of the differentially regulated miRNA are of relevance for transforming growth factor-β signaling and fibrosis, but need to be validated in independent studies.
    The Journal of Rheumatology 11/2014; 42(2). DOI:10.3899/jrheum.140502 · 3.19 Impact Factor

  • [Show abstract] [Hide abstract]
    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; 67(6). DOI:10.1002/acr.22520
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: Autoimmunity may in part result from deficiencies in the processing of apoptotic debris. As mannose-binding lectin (MBL) is involved in such processes, we hypothesized that the variants in the MBL2 gene resulting in MBL deficiency confer an increased risk of nephritis in systemic lupus erythematosus (SLE). Methods: A total of 171 SLE patients attending a Danish tertiary rheumatology referral center were included. Common variant alleles in exon 1 of the MBL2 gene (R52C, rs5030737; G54D, rs1800450; G57E, rs1800451) were genotyped. The normal allele and variant alleles are termed A and O, respectively. The follow-up period was defined as the time from fulfillment of the ACR 1987 classification criteria for SLE until the occurrence of an event (nephritis, end-stage renal disease (ESRD), or death) or end of follow-up. Cox regression analyses were controlled for gender, age and race. Results: During a median follow-up of 5.7 years, nephritis developed in 94 patients, and ESRD developed in 16 of these patients. Twenty-seven patients died. The distribution of the MBL2 genotypes A/A, A/O and O/O was 58%, 35% and 7.0%, respectively. Compared to the rest, O/O patients had 2.6 times (95% CI: 1.2-5.5) higher risk of developing nephritis, and their risk of death after 10 years was 6.0 times increased (95% CI: 1.0-36). MBL serum levels below 100 ng/ml were associated with a 2.0 (95% CI: 1.2-3.4; p = 0.007) increased risk of developing nephritis. ESRD and histological class of nephritis were not associated with MBL deficiency. Conclusions: Genetically determined MBL deficiency was associated with development of nephritis in SLE patients, but not with histological class of nephritis or ESRD.
    Lupus 10/2014; 23(11):1105-1111. DOI:10.1177/0961203314536478 · 2.20 Impact Factor
  • Source

    Arthritis Research & Therapy 09/2014; 16(Suppl 1):A35-A35. DOI:10.1186/ar4651 · 3.75 Impact Factor
  • [Show abstract] [Hide abstract]
    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 · 2.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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; 24(1). DOI:10.1177/0961203314547791 · 2.20 Impact Factor
  • [Show abstract] [Hide abstract]
    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 · 2.97 Impact Factor
  • Helene Bisgaard · Søren Jacobsen · Niels Tvede · Jens Langhoff-Roos ·
    [Show abstract] [Hide abstract]
    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).
  • [Show abstract] [Hide abstract]
    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 · 3.48 Impact Factor

Publication Stats

6k Citations
767.62 Total Impact Points


  • 2015
    • Rigshospitalet
      København, Capital Region, Denmark
  • 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
  • 2011
    • University of Copenhagen Herlev Hospital
      Herlev, Capital Region, Denmark
  • 1993-2010
    • Copenhagen University Hospital Hvidovre
      • Department of Radiology
      Hvidovre, Capital Region, Denmark
  • 2002-2009
    • Bispebjerg Hospital, Copenhagen University
      • Department of Dermatology
      København, Capital Region, Denmark
  • 2008
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain
    • National University (California)
      San Diego, California, United States
  • 2000-2004
    • Statens Serum Institut
      • Department of Epidemiology Research
      København, Capital Region, Denmark
  • 1989-1997
    • Frederiksberg Hospital
      Фредериксберг, Capital Region, Denmark