Change search
Refine search result
1 - 33 of 33
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Bengtsson, C.
    et al.
    Department of Rheumatology, Östersund Hospital, Sweden .
    Bengtsson, A. A.
    Department of Rheumatology, Institute of Clinical Sciences, Lund University Hospital, Sweden .
    Costenbader, K. H.
    Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA .
    Jönsen, A.
    2Department of Rheumatology, Institute of Clinical Sciences, Lund University Hospital, Sweden .
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Sturfelt, G.
    Department of Rheumatology, Institute of Clinical Sciences, Lund University Hospital, Sweden .
    Nived, O.
    Department of Rheumatology, Institute of Clinical Sciences, Lund University Hospital, Sweden .
    Systemic lupus erythematosus and cardiac risk factors: medical record documentation and patient adherence2011In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 20, no 10, p. 1057-1062Article in journal (Refereed)
    Abstract [en]

    This study explores patients' knowledge of cardiac risk factors (CRFs), analyses how information and advice about CRFs are documented in clinical practice, and assesses patient adherence to received instructions to decrease CRFs. Systemic lupus erythematosus (SLE) patients with >= 4 ACR criteria participated through completing a validated cardiovascular health questionnaire (CHQ). Kappa statistics were used to compare medical records with the self-reported CHQ (agreement) and to evaluate adherence. Two hundred and eleven (72%) of the known patients with SLE participated. The mean age of the patients was 55 years. More than 70% of the SLE patients considered hypertension, obesity, smoking and hypercholesterolaemia to be very important CRFs. The agreement between medical record documentation and patients' reports was moderate for hypertension, overweight and hypercholesterolaemia (kappa 0.42-0.60) but substantial for diabetes (kappa 0.66). Patients' self-reported adherence to advice they had received regarding medication was substantial to perfect (kappa 0.65-1.0). For lifestyle changes in patients with hypertension and overweight, adherence was only fair to moderate (kappa 0.13-0.47). Swedish SLE patients' awareness of traditional CRFs was good in this study. However, the agreement between patients' self-reports and medical record documentation of CRF profiles, and patients' adherence to medical advice to CRF profiles, could be improved. Lupus (2011) 20, 1057-1062.

  • 2. Bengtsson, C
    et al.
    Öhman, Marie-Louise
    Nived, O
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Cardiovascular event in Systemic Lupus Erythematosus in northern Sweden: incidence and predictors in a 7-year follow up study2012In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 21, no 4, p. 452-459Article in journal (Refereed)
    Abstract [en]

    Introduction. An increased rate of cardiovascular disease (CVD) has been suggested in patients with systemic lupus erythematosus (SLE). The risk for myocardial infarction (MI), coronary artery disease and stroke has been reported as particularly prevalent in younger females compared with the reference population. This study was performed to analyse the standard incidence ratio (SIR) of and predictors for cardiovascular events (CVEs) in patients with SLE from northern Sweden, with a fairly homogenous population.

    Methods. In 2000 all prevalent patients with SLE (≥4 American College of Rheumatology [ACR] criteria; n = 277) from the four northern-most counties of Sweden were assessed with clinical and laboratory analyses. Seven years follow-up data concerning MI and stroke were extracted from the national registers of hospitalization and death in Sweden. The incidence ratio among the patients was compared with that for the general population from the same catchment area using data from the same register and Statistics Sweden. To identify time to event and CVE predictors, two matched controls for each patient were used and disease related variables as CVD predictors.

    Results. The SIR for a CVE was 1.27 (95% CI 0.82-1.87) and for females separately aged 40-49 years was 8.00 (95% CI 1.65-23.38). The overall SIR for MI was 2.31 (95% CI 1.34-3.7), for females overall was 1.75 (95% CI 0.84-3.22) and for females aged between 40 and 49 years was 8.7 (95% CI 1.1-31.4). The time to an event was significantly shorter among SLE patients (p < 0.001) and was predicted by hypertension adjusted for smoking and disease. High SLEDAI and anti-cardiolipin IgG antibodies predicted an event in Cox proportional hazards regression models adjusted for age and previous MI. Diabetes, smoking ever and sex did not affect the prediction models.

    Conclusion. The risk of a CVE, or MI, was eight- or nine-fold greater among middle-aged female SLE patients. Time to event was significantly shorter and CVE was associated with SLE-related factors including hypertension and age.

  • 3.
    Bentow, C.
    et al.
    Inova Diagnost, CA USA.
    Lakos, G.
    Inova Diagnost, CA USA.
    Martis, P.
    Inova Diagnost, CA USA.
    Wahl, E.
    Inova Diagnost, CA USA.
    Garcia, M.
    Hospital Clin Barcelona, Spain.
    Vinas, O.
    Hospital Clin Barcelona, Spain.
    Espinosa, G.
    Hospital Clin Barcelona, Spain.
    Cervera, R.
    Hospital Clin Barcelona, Spain.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Carmona-Fernandes, D.
    University of Lisbon, Portugal.
    Santos, M. J.
    University of Lisbon, Portugal.
    Hanly, J. G.
    Dalhousie University, Canada.
    Mahler, M.
    Inova Diagnost, CA USA.
    International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies2016In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 25, no 8, p. 864-872Article in journal (Refereed)
    Abstract [en]

    Objective: Anti-double stranded desoxyribonucleic acid (anti-dsDNA) antibodies are considered fairly specific for systemic lupus erythematosus (SLE) and their quantification is useful for the clinical management of SLE patients. We assessed the diagnostic performance of the QUANTA Flash dsDNA chemiluminescent immunoassay (CIA) in comparison to an ELISA, using patients from five participating countries. The main focus was to evaluate the correlation between anti-dsDNA antibody results from the CIA and global SLE disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). Patients and methods: A total of 1431 samples (SLE, n=843; disease controls, n=588) from five countries (Canada, USA, Portugal, Sweden and Spain) were tested with QUANTA Flash dsDNA (Inova Diagnostics, San Diego, CA, USA). Data obtained with the QUANTA Lite dsDNA SC ELISA (Inova Diagnostics) were available for samples from three sites (Canada, USA and Sweden, n=566). The SLEDAI-2K scores were available for 805 SLE patients and a cut-off ofamp;gt;4 was used to define active disease. Results: QUANTA Flash dsDNA had a sensitivity of 54.3% for the diagnosis of SLE, combined with 89.8% specificity. Anti-dsDNA antibody levels were significantly higher (pamp;lt;0.0001) in active SLE (SLEDAI-2Kamp;gt;4; n=232; median value 83.0IU/mL) versus the inactive patients (n=573; median value 22.3IU/mL), and the SLEDAI-2K scoring correlated with their dsDNA antibody levels (Spearmans rho=0.44, pamp;lt;0.0001). Similar but less pronounced findings were also found for the ELISA, in relation to disease activity. Conclusions: The QUANTA Flash dsDNA assay showed good clinical performance in a large international multi-center study. Additionally, the strong correlation between anti-dsDNA antibody results and SLEDAI-2K scores supported the potential utility of QUANTA Flash dsDNA for monitoring disease activity.

  • 4.
    Blomberg, Stina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eloranta, Maija-Leena
    Cederblad, Brita
    Nordlin, K
    Alm, G.V.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Presence of cutaneous interferon-alpha producing cells in patients with systemic lupus erythematosus2001In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 10, no 7, p. 484-90Article in journal (Refereed)
    Abstract [en]

    Systemic lupus erythematosus (SLE) patients have increased levels of interferon-alfa (IFN-alpha) in the circulation but a reduced number of functionally intact natural IFN-alpha producing cells (IPC) in peripheral blood. In search for tissue localisation of activated IPC, we investigated skin biopsies from SLE patients for the occurrence of such cells. Eleven SLE patients with inflammatory skin lesions and six healthy controls were biopsied. An immunohistochemical technique (IH) and in situ hybridisation (ISH) were used to detect intracellular IFN-alpha protein and IFN-alpha mRNA, respectively. In all 11 biopsies from SLE lesions, a high number of IPC were detected by IH. In the nonlesional SLE biopsies we could also demonstrate IPC in 10/11 patients. In 6/11 SLE patients, IFN-alpha mRNA containing cells could be detected in the specimens. A low number of IPC were detected in 1/6 healthy controls by IH, but no ISH positive cells were seen. Our results demonstrate that SLE patients have active IPC in both dermal lesions and in noninflammatory skin. A recruitment of IPC from blood to peripheral tissues may explain the low number of circulating natural IPC in SLE patients. Because the type I IFN system is involved in the SLE disease process, these results are of interest for the understanding of the pathogenesis in SLE.

  • 5. Brodszki, J
    et al.
    Bengtsson, C
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Nived, O
    Sturfelt, G
    Marsal, K
    Abnormal mechanical properties of larger arteries in postmenopausal women with systemic lupus erythematosus2004In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 13, no 12, p. 917-923Article in journal (Refereed)
    Abstract [en]

    There is limited knowledge of potential defects in arterial wall properties in female systemic lupus erythematosus (SLE) patients without manifest cardiovascular disease (CVD) and significant atherosclerotic lesions. The aim of the present study was to investigate the mechanical properties of larger vessels in these patients and to compare them with healthy controls. B-mode ultrasound was used to assess vessel wall structure and to exclude presence of plaque. The ankle/brachial pressure index was measured to exclude occlusive arterial disease. An ultrasound echo-tracking system was used to determine stiffness of the abdominal aorta, common carotid artery (CCA) and popliteal artery (PA) in 39 female patients with SLE and 55 female, healthy controls. SLE had an independent effect on stiffening of the CCA (P = 0.01) and PA (P = 0.005). In addition, larger vessel diameters were observed in the CCA (P = 0.002) after adjustments for the effects of mean arterial pressure and age. Thus, this investigation demonstrated an increased arterial stiffness and signs of premature vascular ageing in the SLE patients without manifest cardiovascular disease and without significant atherosclerotic lesions. The results of this study indicate that other mechanisms besides atherosclerosis might be involved in the pathogenesis of arterial stiffening in SLE patients.

  • 6. Checa, A.
    et al.
    Idborg, H.
    Zandian, A.
    Sar, D. Garcia
    Surowiec, Izabella
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Svenungsson, E.
    Jakobsson, P-J
    Nilsson, P.
    Gunnarsson, I.
    Wheelock, C. E.
    Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study2017In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 26, no 10, p. 1023-1033Article in journal (Refereed)
    Abstract [en]

    Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus.

    Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease.

    Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C-16:0-ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C-16:0-ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C-16:0- and C-24:1-hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment.

    Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated with disease activity. This study demonstrates the utility of simultaneously targeting multiple components of a pathway to establish disease associations.

  • 7. Checa, A.
    et al.
    Idborg, H.
    Zandian, Arash
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sar, D. Garcia
    Surowiec, I.
    Trygg, J.
    Svenungsson, E.
    Jakobsson, P-J
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Gunnarsson, I.
    Wheelock, C. E.
    Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study2017In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 26, no 10, p. 1023-1033Article in journal (Refereed)
    Abstract [en]

    Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease. Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C-16:0-ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C-16:0-ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C-16:0- and C-24:1-hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment. Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated with disease activity. This study demonstrates the utility of simultaneously targeting multiple components of a pathway to establish disease associations.

  • 8.
    Dahlström, Örjan
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    The diagnostic accuracies of the 2012 SLICC criteria and the proposed EULAR/ACR criteria for systemic lupus erythematosus classification are comparable2019In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 28, no 6, p. 778-782Article in journal (Refereed)
    Abstract [en]

    In a joint effort, the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) recently proposed new criteria for the classification of systemic lupus erythematosus (SLE) with the overarching goal to identify potential participants for clinical studies. Herein, we present the first independent evaluation of these criteria in comparison with older classification grounds using an adult Scandinavian study population of confirmed SLE cases and individuals with SLE-mimicking conditions. We included 56 confirmed SLE cases meeting the 1982 ACR criteria (ACR-82) and/or the Fries diagnostic principle (antinuclear antibodies on at least one occasion plus involvement of at least two defined organ systems) and 55 controls with possible systemic autoimmune disease, including the presence of any SLE-related autoantibody. The proposed EULAR/ACR criteria showed a diagnostic sensitivity of 93% (95% confidence interval (CI), 0.83-0.98) compared with 83% (95% CI, 0.72-0.91) for the updated ACR criteria from 1997. The diagnostic accuracy of all tested classification grounds was fairly similar, achieving approximately 85%. However, the disease specificity of the EULAR/ACR criteria reached only 73% (95% CI, 0.59-0.83), which was comparable with the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria, 75% (95% CI, 0.61-0.85), but clearly lower than for ACR-82, 94% (95% CI, 0.83-0.99). In this first independent evaluation of a limited number of cases, we found comparable results with respect to diagnostic sensitivity, specificity and accuracy regarding the SLICC-12 and the proposed EULAR/ACR classification criteria. However, their specificity for SLE appeared to be lower compared with ACR-82.

  • 9.
    Eriksson, Catharina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Eneslätt, Kjell
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Ivanoff, J
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Sundqvist, Karl-Gösta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Abnormal expression of chemokine receptors on T-cells from patients with systemic lupus erythematosus2003In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 12, no 10, p. 766-774Article in journal (Refereed)
    Abstract [en]

    The expression of chemokine receptors on T-cells and chemokine levels in the blood was studied in 23 patients with SLE (ACR criteria), seven patients with rheumatoid arthritis (RA) and in 15 healthy controls using flow cytometry, RT-PCR and ELISA. The cell surface expression of the chemokine receptors CXCR5 and CCR6 was decreased in SLE patients compared with controls (P = 0.051 and P = 0.002, respectively). The decrease of CXCR5 was confined to SLE patients with inactive disease (SLEDAI < 6) compared with active disease (SLEDAI &GE; 6) and controls. CXCR2 and CCR1 were increased in patients with active SLE compared with patients with inactive disease (P = 0.001 and P = 0.01, respectively) and with controls ( P = 0.02 and P = 0.053, respectively). The levels of the chemokines MIP-1β MCP-1, SDF-1α, IP-10 and RANTES were significantly elevated in SLE patients compared with controls. Patients with renal involvement had increased surface expression of CXCR3 and CCR3 (P = 0.04 in both) and a lower level of soluble IP-10 compared with patients without renal disease (P = 0.025) and compared with controls (P = 0.001). The ratio between CCR5 and CCR3 was significantly increased in RA patients compared with SLE patients and controls supporting a Th1 overweight in RA. In conclusion, patients with SLE showed abnormal T-cell expression of several chemokine receptors and levels of soluble chemokines in their plasma/ serum.

  • 10.
    Eriksson, Catharina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Cytokines in relation to autoantibodies before onset of symptoms for systemic lupus erythematosus2014In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 23, no 7, p. 691-696Article in journal (Refereed)
    Abstract [en]

    Objectives: A number of cytokines and chemokines were analysed and related to autoantibodies in blood samples pre-dating the onset of symptoms of systemic lupus erythematosus. Methods: Thirty-five patients with systemic lupus erythematosus (American College of Rheumatology criteria) were identified as having donated blood samples, prior to symptom onset, to the Biobank of northern Sweden. Altogether, 140 age-and sex-matched controls were also identified. The concentrations of interferon-a, interleukin-4, interleukin-9, interleukin-10, interferon inducible protein-10 and monocyte chemotactic protein-1 were analysed using multiplex technology and related to autoantibodies (ANA, ENA, anti-dsDNA and anti-histone antibodies) analysed from the same blood sample. Results: The interferon-g inducible protein-10 levels were higher in the pre-symptomatic individuals than in controls (p < 0.05) and correlated with interferon-a (p < 0.01). The interferon-g inducible protein-10 and interferon-a concentrations were significantly increased in individuals positive for autoantibodies: interferon-g inducible protein-10 for ANA; anti-SSA/Ro and anti-Jo-1 antibodies; interferon-a with anti-SSB/La antibodies. The levels of interleukin-10, interferon-g inducible protein-10 and monocyte chemotactic protein-1 increased significantly from the pre-symptomatic individuals to after onset of systemic lupus erythematosus. Conclusions: An increased concentration of interferon-gamma inducible protein-10 pre-dated the onset of systemic lupus erythematosus and was related to autoantibodies before the onset of disease. The levels of interferon-gamma inducible protein-10 and interferon-alpha were correlated. These findings support the proposal that the interferon system is important early in the pathogenesis of systemic lupus erythematosus and autoantibody formation.

  • 11.
    Ferrannini, Giulia
    et al.
    Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden.;Univ Turin, Postgrad Sch Internal Med, Dept Med Sci, Turin, Italy..
    Svenungsson, Elisabet
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Rheumatol Unit, Stockholm, Sweden..
    Kjellstrom, Barbro
    Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden..
    Elvin, Kerstin
    Karolinska Inst, Dept Clin Immunol & Transfus Med, Unit Clin Immunol, Stockholm, Sweden..
    Grosso, Giorgia
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Rheumatol Unit, Stockholm, Sweden..
    Näsman, Per
    KTH, School of Architecture and the Built Environment (ABE), Real Estate and Construction Management, Building and Real Estate Economics.
    Ryden, Lars
    Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden..
    Norhammar, Anna
    Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden.;Capio St Gorans Hosp, Stockholm, Sweden..
    Dysglycaemic patients with antiphospholipid antibodies IgG: a neglected group at high cardiovascular risk?2019In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 28, p. 42-42Article in journal (Other academic)
  • 12.
    Frodlund, M.
    et al.
    Linkoping Univ, Dept Clin & Expt Med, Div Neuro & Inflammat Sci, Linkoping, Sweden.
    Reid, Sarah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wettero, J.
    Linkoping Univ, Dept Clin & Expt Med, Div Neuro & Inflammat Sci, Linkoping, Sweden.
    Dahlstrom, O.
    Linkoping Univ, Swedish Inst Disabil Res, Dept Behav Sci & Learning, Linkoping, Sweden.
    Sjowall, C.
    Linkoping Univ, Dept Clin & Expt Med, Div Neuro & Inflammat Sci, Linkoping, Sweden.
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The majority of Swedish systemic lupus erythematosus patients are still affected by irreversible organ impairment: factors related to damage accrual in two regional cohorts2019In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 28, no 10, p. 1261-1272, article id UNSP 0961203319860198Article in journal (Refereed)
    Abstract [en]

    Background Although the survival of patients with systemic lupus erythematosus (SLE) has improved, irreversible organ damage remains a critical concern. We aimed to characterize damage accrual and its clinical associations and causes of death in Swedish patients. Methods Accumulation of damage was evaluated in 543 consecutively recruited and well-characterized cases during 1998-2017. The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology damage index (SDI) was used to estimate damage. Results Organ damage (SDI >= 1) was observed in 59%, and extensive damage (SDI >= 3) in 25% of cases. SDI >= 1 was significantly associated with higher age at onset, SLE duration, the number of fulfilled SLICC criteria, neurologic disorder, antiphospholipid antibody syndrome (APS), hypertension, hyperlipidemia, depression and secondary Sjogren's syndrome (SS). In addition, SDI >= 3 was associated with serositis, renal and haematological disorders and interstitial lung disease. A multiple regression model identified not only well-known risk factors like APS, antihypertensives and corticosteroids, but pericarditis, haemolytic anaemia, lymphopenia and myositis as being linked to SDI. Malignancy, infection and cardiovascular disease were the leading causes of death. Conclusions After a mean SLE duration of 17 years, the majority of today's Swedish SLE patients have accrued damage. We confirm previous observations and report some novel findings regarding disease phenotypes and damage accrual.

  • 13.
    Frodlund, Martina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Reid, S.
    Uppsala Univ, Sweden.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Dahlström, Örjan
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Leonard, D.
    Uppsala Univ, Sweden.
    The majority of Swedish systemic lupus erythematosus patients are still affected by irreversible organ impairment: factors related to damage accrual in two regional cohorts2019In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, article id UNSP 0961203319860198Article in journal (Refereed)
    Abstract [en]

    Background Although the survival of patients with systemic lupus erythematosus (SLE) has improved, irreversible organ damage remains a critical concern. We aimed to characterize damage accrual and its clinical associations and causes of death in Swedish patients. Methods Accumulation of damage was evaluated in 543 consecutively recruited and well-characterized cases during 1998-2017. The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology damage index (SDI) was used to estimate damage. Results Organ damage (SDI amp;gt;= 1) was observed in 59%, and extensive damage (SDI amp;gt;= 3) in 25% of cases. SDI amp;gt;= 1 was significantly associated with higher age at onset, SLE duration, the number of fulfilled SLICC criteria, neurologic disorder, antiphospholipid antibody syndrome (APS), hypertension, hyperlipidemia, depression and secondary Sjogrens syndrome (SS). In addition, SDI amp;gt;= 3 was associated with serositis, renal and haematological disorders and interstitial lung disease. A multiple regression model identified not only well-known risk factors like APS, antihypertensives and corticosteroids, but pericarditis, haemolytic anaemia, lymphopenia and myositis as being linked to SDI. Malignancy, infection and cardiovascular disease were the leading causes of death. Conclusions After a mean SLE duration of 17 years, the majority of todays Swedish SLE patients have accrued damage. We confirm previous observations and report some novel findings regarding disease phenotypes and damage accrual.

  • 14. Frostegård, J.
    et al.
    Hellström, Cecilia
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Frostegård, A. G.
    Ajeganova, S.
    Autoantibody profiling reveals four protein candidate autoantigens associated with systemic lupus erythematosus2018In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 27, no 10, p. 1670-1678Article in journal (Refereed)
    Abstract [en]

    Objectives In systemic lupus erythematosus (SLE) there are typically many autoantibodies. The disease heterogeneity could be better understood with discovery of phenotype-specific antigens targeted by autoantibodies. We here aimed to identify novel autoantigens potentially related to SLE disease and a major complication, atherosclerosis. Methods Antigen microarrays were used to profile IgG autoantibody reactivity against 77 protein fragments (20-140 amino acids (aa) long, median 89 aa) produced within the Human Protein Atlas project, in serum samples from SLE patients (n=107) and age- and sex-matched population-based controls (n=107). Common carotid intima-media thickness, plaque occurrence and echogenicity were determined by B-mode ultrasound. Results We determined significant differences between patients and controls in IgG reactivity against four proteins. In patients compared to controls, there was an increase of IgG reactivity against zinc finger protein 688 (ZNF688), early B cell factor 2 (EBF2), crystallin, alpha B (CRYAB) and tumor necrosis factor receptor superfamily member 13C (TNFRSF13C). Of these four antigens, only anti-ZNF688 was associated with carotid atherosclerosis (plaque occurrence) and vulnerable plaques in SLE. There was a weak association between anti-EBF2 and SLE disease activity but no significant associations were determined for other measured IgG reactivity. Conclusions In this discovery screening we here demonstrate new candidate autoantigens with differential reactivity (reflecting autoantibody levels) in SLE patients and in controls and in relation to atherosclerosis in SLE.

  • 15. Jin, T
    et al.
    Almehed, K
    Carlsten, H
    Forsblad-d'Elia, Helena
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Decreased serum levels of TGF-β1 are associated with renal damage in female patients with systemic lupus erythematosus.2012In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 21, no 3Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Transforming growth factor β1 (TGF-β1) has a large role in the control of autoimmunity. TGF-β1 production by lymphocytes is reduced in systemic lupus erythematosus (SLE). Decreased levels of TGF-β1 might associate to disease susceptibility, activity and organ damage in SLE. However, the correlation between TGF-β1 levels and severity of renal damage in SLE has not been examined.

    METHODS: The present study was undertaken to assess the serum levels of total and active TGF-β1 in 150 female patients with SLE and 31 healthy women. Simple and multiple regression analyses between TGF-β1 levels and the diseases-related variables were performed in patients with SLE.

    RESULTS: Serum levels of both total and active TGF-β1 were significantly reduced in patients with SLE compared with levels in healthy controls (p < 0.01). Total TGF-β1 levels correlated positively with white blood cell, platelet counts, calculated glomerular filtration rate (GFR), and active TGF-β1 level, and inversely with erythrocyte sedimentation rate (ESR). In multiple regression analysis, ESR and platelet counts remained determinants of total TGF-β1. Total TGF-β1 levels were lower in patients with high disease activity (SLEDAI > 10) and severe organ damage (SLICC > 3). Significantly lower levels of total TGF-β1 were found in patients with severe renal damage, i.e. lower TGF-β1 in patients with 24-h urine protein over 3.5 g than in those with below 3.5 g (p < 0.05); lower TGF-β1 in patients with GFR less than 50 ml/min than in those with over 50 ml/min (p < 0.05). In contrast, active TGF-β1 only correlated with platelet counts. There was no association between renal damage and the levels of active TGF-β1.

    CONCLUSION: This study demonstrates significantly reduced serum levels of both total and active TGF-β1 in women with SLE compared with healthy women. Total TGF-β1 levels are correlated negatively with ESR and positively with blood platelets. Total TGF-β1 levels were lower in SLE patients with high disease activity and severe organ damage. Importantly, the severity of the renal damage was associated with decreased serum levels of total TGF-β1, suggesting that TGF-β1 might be involved in pathogenesis of renal damage caused by lupus nephritis.

  • 16. Jonsen, A
    et al.
    Bengtsson, AA
    Nived, O
    Ryberg, B
    Truedsson, L
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Alm, GV
    Sturfelt, G
    The heterogeneity of neuropsychiatric systemic lupus erythematosus isreflected in lack of association with cerebrospinal fluid cytokineprofiles2003In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 12, no 11, p. 846-850Article in journal (Refereed)
    Abstract [en]

    The objective was to study the occurrence of autoantibodies and cytokines in serum and cerebrospinal fluid (CSF) in neuropsychiatric systemic lupus erythematosus (NPSLE). In total, 28 consecutive patients with NPSLE and 16 systemic lupus erythematosus (SLE) patients without neuropsychiatric involvement (non-NPSLE) were studied. IFN-alpha, IL-6, IL-10, soluble terminal complement complex (TCC), anti-ribosomal P protein antibodies (anti-P) and anti-cardiolipin antibodies (aCL) were measured in serum and CSF by immunoassays. Analyses of white blood cell differential count, CSF-albumin/serum-albumin ratio, IgG-index in CSF and isoelectric focusing in serum and CSF were also performed. CSF specimens from 23 healthy individuals were used as controls. IFN-alpha was elevated in the CSF of 5 of 28 NPSLE patients compared to three of 14 among the non-NPSLE patients. IL-6 was elevated in CSF in three of 26 NPSLE patients. Normal concentration of IL-10 was found in CSF in all 27 NPSLE-patients analysed. IFN-alpha in serum was elevated in 18 of 28 NPSLE patients. No distinct clinical phenotype was related to elevated cytokine concentration in serum or CSF. One patient with cerebral involvement complicated by progressive multifocal leukoencephalopathy displayed a very high IFN-alpha concentration in serum. High concentration of TCC was present in CSF from only one patient with systemic vasculitis and focal cerebral symptoms. In conclusion, the results of this study suggest that the diagnostic value of serum and CSF concentrations of IFN-alpha, IL-10, IL-6 and TCC is limited in unselected neuropsychiatric SLE, probably due to the heterogeneity of NPSLE pathogenesis.

  • 17. Meroni, Pier Luigi
    et al.
    Tincani, A.
    Alarcón-Riquelme, Marta E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Shoenfeld, Y.
    Borghi, M. O.
    European Forum on Antiphospholipid Antibodies: research in progress2009In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 18, no 10, p. 924-929Article in journal (Refereed)
    Abstract [en]

    The research projects of the European Forum on Antiphospholipid Antibodies are representative of how dynamic is this area of investigation. The present review is focused on the most recent projects of the Forum on the aetiopathogenic aspects of the antiphospholipid syndrome (APS). Studies on the genetic background of the APS are ongoing in order to better define the proximity between APS and full-blown systemic lupus erythematosus. However, the analysis of the polymorphisms of genes coding for inflammatory mediators may offer new information on the role of inflammatory processes in triggering thrombotic events as well as the whole susceptibility for developing the vascular manifestations. A systematic and wide detection of serological markers of infectious processes will give new insight on the role of infectious agents in favouring autoimmunity in APS. Owing to the well-known role of vitamin D(3) defect in autoimmune disease, the detection of vitamin plasma levels in APS patients will offer the rationale for a possible therapeutic supplementation. Additional projects are aimed to better characterize the diagnostic/prognostic value of antiphospholipid antibodies (aPL) by defining their epitope specificity and binding avidity. Pregnancy complications represent the obstetric side of APS. Research projects are focussed on the role of complement activation in placenta damage and on the potential ability of aPL to affect the fertility. Finally, a study has been planned in order to draw definitive conclusions on the associations between aPL and atherosclerosis.

  • 18.
    Moraes-Fontes, M. F.
    et al.
    Ctr Hosp Lisboa Cent, Hosp Curry Cabral, Unidade Doencas Autoimunes, Lisbon, Portugal..
    Berntsson, Shala G.
    Akad Sjukhuset Uppsala, Uppsala, Sweden..
    Comment on: PML in patients with systemic lupus erythematosus: a systematic literature review2017In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 26, no 1, p. 106-106Article in journal (Refereed)
  • 19. Parodis, I.
    et al.
    Axelsson, M.
    KTH.
    Gunnarsson, I.
    Belimumab for systemic lupus erythematosus: a practice-based view2013In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 22, no 4, p. 372-380Article in journal (Refereed)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with multiple organ involvement. B-lymphocyte activity plays a pivotal role in the development and course of the disease. A newly developed agent called belimumab has recently been approved to treat active, autoantibody positive SLE as an add-on to standard therapy. Specifically binding to soluble B-lymphocyte stimulator protein, it reduces the formation of immunoglobulins and autoantibodies. Its effects have been studied in one phase II and two phase III clinical trials, showing sustained improvement across various clinical indicators and no evidence of increased risk of serious adverse events. Further post-hoc analyses indicate that treatment with belimumab lowers levels of autoimmune antibodies, normalizes low complement and improves SLE activity predominantly in musculoskeletal and mucocutaneous organ domains. Further studies are needed to determine the efficacy of belimumab for patients with severe lupus nephritis and with active involvement of the central nervous system. The introduction of belimumab as the first biological drug approved for the management of SLE likely heralds a surge in the development and use of selectively addressed agents for this heterogeneous and complex disease.

  • 20.
    Pettersson, Susanne
    et al.
    Rheumatology Clinic, Karolinska University Hospital, Stockholm, Sweden Division of Nursing, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden .
    Boström, Carina
    Division of Physiotherapy, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Eriksson, Karin
    Division of Physiotherapy, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Svenungsson, Elisabet
    Department of Medicine, Unit of Rheumatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Gunnarsson, Iva
    Department of Medicine, Unit of Rheumatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Welin Henriksson, Elisabet
    Rheumatology Clinic, Karolinska University Hospital, Stockholm, Sweden Division of Nursing, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Lifestyle habits and fatigue among people with systemic lupus erythematosus and matched population controls2015In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 24, no 9, p. 955-965Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The objective of this paper is to identify clusters of fatigue in patients with systemic lupus erythematosus (SLE) and matched controls, and to analyze these clusters with respect to lifestyle habits, health-related quality of life (HRQoL), anxiety and depression.

    METHODS: Patients with SLE (n = 305) and age- and gender-matched population controls (n = 311) were included. Three measurements of fatigue (Fatigue Severity Scale (FSS), Vitality (VT, from SF-36) and Multidimensional Assessment of Fatigue scale (MAF) and hierarchic cluster analysis were used to define clusters with different degrees of fatigue. Lifestyle habits were investigated through questionnaires. HRQoL was assessed with the SF-36 and anxiety/depression with the Hospital Anxiety and Depression Scale.

    RESULTS: Three clusters, denominated "High," "Intermediate" and "Low" fatigue clusters, were identified. The "High" contained 80% patients, and 20% controls (median; VT 25, FSS 5.8, MAF 37.4). These had the most symptoms of depression (51%) and anxiety (34%), lowest HRQoL (p < 0.001) and they exercised least frequently. The "Intermediate" (48% patients and 52% controls) (median; VT 55, FSS 4.1, MAF 23.5) had similarities with the "Low" regarding sleep/rest whereas social status and smoking were closer to the "High." The"Low" contained 22% patients and 78% controls (median; VT 80, FSS 2.3, MAF 10.9). They had the highest perceived HRQoL (p < 0.001), least symptoms of anxiety (10%), no depression, smoked least (13%) and reported the highest percentage (24%) of exercising ≥ 3 times/week.

    CONCLUSION: Fatigue is common, but not a general feature of SLE. It is associated with depression, anxiety, low HRQoL and less physical exercise. Patients with SLE and population controls with a healthy lifestyle reported lower levels of fatigue. Whether lifestyle changes can reduce fatigue, which is a major problem for a majority of SLE patients, needs to be further explored.

  • 21. Puurunen, M
    et al.
    Palosuo, T
    Lassila, R
    Anttila, M
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Immunologic and hematologic properties of antiabodies to prothrombin and plasminogen in a mouse model.2001In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 10, p. 108-115Article in journal (Refereed)
  • 22.
    Rönnblom, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pascual, V.
    The innate immune system in SLE: type I interferons and dendritic cells2008In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 17, no 5, p. 394-399Article in journal (Refereed)
    Abstract [en]

    Patients with systemic lupus erythematosus (SLE) have an increased expression of type I interferon (IFN) regulated genes because of a continuous production of IFN-alpha. The cellular and molecular background to this IFN-alpha production has started to be elucidated during the last years, as well as the consequences for the innate and adaptive immune systems. Plasmacytoid dendritic cells (pDC) activated by immune complexes containing nucleic acids secrete type I IFN in SLE. Type I IFN causes differentiation of monocytes to myeloid-derived dendritic cell (mDC) and activation of autoreactive T and B cells. A new therapeutic option in patients with SLE is, therefore, inhibition of IFN-alpha, and recent data from a phase I clinical trial suggests that administration of neutralizing monoclonal antibodies against anti-IFN-alpha can ameliorate disease activity.

  • 23.
    Sippl, Natalie
    et al.
    Karolinska Inst, Rheumatol Unit, Dept Med Solna, Karolinska Univ Hosp, Stockholm, Sweden..
    Grosso, Giorgia
    Karolinska Inst, Rheumatol Unit, Dept Med Solna, Karolinska Univ Hosp, Stockholm, Sweden..
    Ferrannini, Giulia
    Karolinska Inst, Dept Med Heart & Vasc Theme, Karolinska Univ Hosp, Stockholm, Sweden..
    de Faire, Ulf
    Karolinska Inst, Div Cardiovasc Epidemiol, IMM, Stockholm, Sweden..
    Lindahl, Bertil
    Karolinska Inst, Dept Clin Immunol & Transfus Med, Unit Clin Immunol, Karolinska Univ Hosp, Stockholm, Sweden..
    Näsman, Per
    KTH, School of Architecture and the Built Environment (ABE), Real Estate and Construction Management, Building and Real Estate Economics.
    Norhammar, Anna
    Karolinska Inst, Dept Med Heart & Vasc Theme, Karolinska Univ Hosp, Stockholm, Sweden.;Capio St Gorans Hosp, Stockholm, Sweden..
    Ryden, Lars
    Karolinska Inst, Dept Med Heart & Vasc Theme, Karolinska Univ Hosp, Stockholm, Sweden..
    Svenungsson, Elisabet
    Karolinska Inst, Rheumatol Unit, Dept Med Solna, Karolinska Univ Hosp, Stockholm, Sweden..
    Amara, Khaled
    Karolinska Inst, Rheumatol Unit, Dept Med Solna, Karolinska Univ Hosp, Stockholm, Sweden..
    Domain specific anti-beta 2GPI antibodies in patients with First Myocardial Infarction2019In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 28, p. 39-40Article in journal (Other academic)
  • 24.
    Sjöwall, Christopher
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Hjorth, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    Successful treatment of refractory systemic lupus erythematosus using proteasome inhibitor bortezomib followed by belimumab: description of two cases2017In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 26, no 12, p. 1333-1338Article in journal (Refereed)
    Abstract [en]

    Although the putative therapeutic options for patients with systemic lupus erythematosus (SLE) are steadily increasing, refractory disease is indeed a major challenge to many clinicians and patients. The proteasome inhibitor bortezomib - approved for the treatment of multiple myeloma since the beginning of this century - was recently reported successful in twelve cases of refractory SLE by German colleagues. Herein, we describe two Swedish SLE cases with refractory renal and pulmonary manifestations that were rescued by bortezomib as induction of remission followed by monthly doses of belimumab. The patients were carefully monitored with regard to disease activity and renal function. Anti-dsDNA and anti-C1q antibodies, complement proteins and lymphocyte subsets were analysed in consecutive samples. In December 2016, the patients had been in clinical remission post bortezomib administration for a period of 28 and 22 months, respectively. Potential benefits of using belimumab as maintenance therapy to prevent regeneration of autoreactive B cell clones are discussed.

  • 25.
    Sjöwall, Christopher
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Zapf, J
    Friedrich-Alexander University of Erlangen-Nuremberg (FAU), Germany.
    von Löhneysen, S
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Friedrich-Alexander University of Erlangen-Nuremberg (FAU), Germany.
    Magorivska, I
    Friedrich-Alexander University of Erlangen-Nuremberg (FAU), Germany; Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv, Ukraine.
    Biermann, M
    Friedrich-Alexander University of Erlangen-Nuremberg (FAU), Germany.
    Janko, C
    Friedrich-Alexander University of Erlangen-Nuremberg (FAU), Germany; University Hospital Erlangen, Germany.
    Winkler, S
    Friedrich-Alexander University of Erlangen-Nuremberg (FAU), Germany.
    Bilyy, R
    Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv, Ukraine.
    Schett, G
    Friedrich-Alexander University of Erlangen-Nuremberg (FAU), Germany.
    Herrmann, M
    Friedrich-Alexander University of Erlangen-Nuremberg (FAU), Germany.
    Muñoz, L E
    Friedrich-Alexander University of Erlangen-Nuremberg (FAU), Germany.
    Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus2015In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 24, no 6, p. 569-581Article in journal (Refereed)
    Abstract [en]

    In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of well-characterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex- and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the highest activity of systemic lupus erythematosus. Our results show that native circulating IgG complexes from active systemic lupus erythematosus patients expose fucosyl residues and their glycan core is accessible to soluble lectins. Two putative mechanisms may contribute to the increased exposure of these glycans: (1) the canonical N-glycosylation site of the IgG-CH2 domain; (2) an IgG binding non-IgG molecule, like complement or C-reactive protein. In both cases the complexed IgG may be alternatively targeted to lectin receptors of effector cells, e.g. dendritic cells.

  • 26.
    Tingström, Joanna
    et al.
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Hjelmstedt, Anna
    Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Welin Henriksson, Elisabet
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Ambrosi, Aurélie
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Sonesson, Sven-Erik
    Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Wahren-Herlenius, Marie
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Anti-Ro/SSA autoantibody-positive women's experience of information given on the risk of congenital heart block.2016In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 25, no 5, p. 536-542Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Congenital heart block (CHB) may develop in fetuses of women with anti-Ro/SSA autoantibodies, and carries substantial morbidity and mortality. The aim was to evaluate how information on CHB is imparted and identify areas of improvement.

    METHODS: A questionnaire was distributed to anti-Ro/SSA antibody-positive women who had either participated in a surveillance programme but whose expected child did not develop CHB (n = 100, denoted Doppler-Assessed Pregnancies (DAP) group) or given birth to a child with CHB (n = 88, denoted CHB-Affected Pregnancies (CAP) group).

    RESULTS: The response rate was 83% (157/188). Most women received the information on CHB when they were already pregnant (DAP group 60%, CAP group 83%). However, a majority of them would have wanted the information before pregnancy (DAP group 52%, CAP group 56%), and most stated that it would not have influenced their decision to have a child (DAP group 77%, CAP group 58%). The ability to both understand the information and to perceive the information as sufficient were significantly higher when someone trained in paediatric cardiology gave the information.

    CONCLUSIONS: Our findings indicate that information on CHB should be given to women before pregnancy. The data further highlight the importance of having specific knowledge for giving relevant and understandable, yet sufficient information.

  • 27.
    Tingström, Joanna
    et al.
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Hjelmstedt, Anna
    Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Welin Henriksson, Elisabet
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Sonesson, Sven-Erik
    Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Wahren-Herlenius, Marie
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ro/SSA autoantibody-positive pregnancy: reactions to serial fetal Doppler echocardiographic surveillance2015In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 24, no 14, p. 1540-1545Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The risk for congenital heart block (CHB) associated with maternal Ro/SSA autoantibodies is low, but the possibility of treating early stages of disease has seen the introduction of Doppler echocardiographic surveillance programs with serial examinations during the CHB susceptibility weeks of pregnancy. The aim of the present study was to understand how Ro/SSA autoantibody-positive women having undergone Doppler echocardiographic surveillance programs and giving birth to children without CHB experienced their pregnancy and frequent ultrasound examinations.

    METHODS: A validated questionnaire based on data from an interview-study was distributed to Ro/SSA-positive women supervised with Doppler examinations during their pregnancy (n = 100).

    RESULTS: The response rate was 79%. The majority of the women (61%) reported that the increased number of ultrasound examinations influenced their pregnancy, but in a positive way, with qualified information and additional support from health care personnel in conjunction with the examinations. Further, the visits to the clinic provided opportunities to see the ultrasound picture of the expected infant. However, one-third of the women also reported stress in relation to the examinations.

    CONCLUSIONS: Fetal echocardiographic surveillance holds many and predominantly positive effects for Ro/SSA-positive women during pregnancy in addition to the medical advantages.

  • 28.
    Waldheim, E.
    et al.
    Unit of Rheumatology, Karolinska University Hospital, Huddinge,Stockholm, Sweden & Division of Nursing, Department of Neurobiology, Care Science and Society, Karolinska Institutet, Sweden.
    Elkan, A.-C.
    Unit of Rheumatology, Karolinska University Hospital, Huddinge, Stockholm, Sweden & Department of Medicine, Karolinska Institutet, Huddinge, Sweden & Institute of Environmental Medicine, Karolinska Institutet, Sweden.
    Bergman, Stefan
    Research and Development Centre, Spenshult Hospital, Sweden & Department of Rheumatology, Clinical Sciences, Lund University, Sweden.
    Frostegård, J.
    Institute of Environmental Medicine, Unit of Immunology and Chronic Disease, Karolinska Institutet, Sweden.
    Van Vollenhoven, R.
    Unit of Rheumatology, Karolinska University Hospital, Huddinge, Stockholm, Sweden & Department of Medicine, Karolinska Institutet, Solna, Sweden.
    Henriksson, E. W.
    Unit of Rheumatology, Karolinska University Hospital, Huddinge, Stockholm, Sweden & Division of Nursing, Department of Neurobiology, Care Science and Society, Karolinska Institutet, Sweden.
    Extent and characteristics of self-reported pain in patients with systemic lupus erythematosus2013In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 22, no 2, p. 136-143Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Patients' own experiences of subjective symptoms are scarcely covered, and the objective of this study was to investigate the extent and characteristics of self-reported pain in patients with systemic lupus erythematosus (SLE).

    METHODS: This study comprised a cross-sectional design where 84 patients with SLE were asked to complete self-assessments: visual analogue scale of pain and the Short-Form McGill Pain Questionnaire. Medical assessments, including ESR, SLAM, SLEDAI, and SLICC, were also performed.

    RESULTS: Of the study population, 24% reported higher levels of SLE-related pain (≥40 mm on VAS). This group had a significantly shorter disease duration, higher ESR, and higher disease activity, according to the SLAM and SLEDAI, compared to the rest of the study population. This group mainly used the words "tender," "aching," and "burning" to describe moderate and severe pain, and they used a greater number of words to describe their pain. Of the patients with higher levels of pain, 70% reported their present pain as "distressing." The most common pain location for the whole patient population was the joints. Patients rated their disease activity significantly higher than physicians did.

    CONCLUSION: These findings expand the current knowledge of the extent of SLE-related pain and how patients perceive this pain. The results can contribute to affirmative, supportive and caring communication and especially highlight SLE-related pain in patients with a short disease duration and high disease activity.

  • 29.
    Waldheim, E.
    et al.
    Unit of Rheumatology, Karolinska University Hospital, Sweden & Division of Nursing, Department of Neurobiology, Karolinska Institutet, Sweden.
    Elkan, A.-C.
    Innovation and Development SRQ (Swedish Rheumatology Quality Register), Dept. of Rheumatology, Karolinska University Hospital, Sweden & Institute of Environmental Medicine, Karolinska Institutet, Sweden.
    Pettersson, S.
    Unit of Rheumatology, Karolinska University Hospital, Sweden & Division of Nursing, Department of Neurobiology, Karolinska Institutet, Sweden.
    Van Vollenhoven, R.
    Unit of Rheumatology, Karolinska University Hospital, Sweden & Department of Medicine, Solna, Karolinska Institutet, Sweden.
    Bergman, Stefan
    Research and Development Centre, Spenshult Hospital, Sweden & Department of Rheumatology, Clinical Sciences, Lund University, Sweden.
    Frostegård, J.
    Institute of Environmental Medicine, Unit of Immunology and Chronic Disease, Karolinska Institutet, Sweden.
    Welin Henriksson, E.
    Unit of Rheumatology, Karolinska University Hospital, Sweden & Division of Nursing, Department of Neurobiology, Karolinska Institutet, Sweden.
    Health-related quality of life, fatigue and mood in patients with SLE and high levels of pain compared to controls and patients with low levels of pain2013In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 22, no 11, p. 1118-1127Article in journal (Refereed)
    Abstract [en]

    Objective The objective of this paper is to investigate health-related quality of life (HRQoL), fatigue, anxiety and depression in patients with systemic lupus erythematosus (SLE) and higher levels of pain and to compare them to patients with lower levels of pain and controls.

    Method Patients were dichotomized into two groups based on SLE-related pain score on the visual analog scale (VAS): low-pain group (76%, n=64, VAS 0-39 mm) and high-pain group (24%, n=20, VAS 40-100 mm). Sex- and age-matched controls were randomly selected from the general population. Participants were asked to complete questionnaires regarding self-reported pain, HRQoL, fatigue, anxiety and depression. Medical assessments also were recorded.

    Result Fatigue score in the high-pain group (median, 36.5; interquartile range (IQR), 32.5-39.7) was significantly higher (p<0.001) compared to the low-pain group (median, 23; IQR, 14.6-34.1), as well as scores for anxiety (median, 9; IQR, 6.5-11.5) and depression (median, 7.5; IQR, 5.5-9) (p<0.001). The high-pain group had significantly lower scores compared to the low-pain group in all dimensions in the SF-36 (p ≤ 0.001-0.007). No statistical differences were detected between the low-pain group and controls in any measurement except for the dimensions physical function, general health, vitality and social function in SF-36.

    Conclusion Patients with SLE scoring higher degrees of pain were burdened with more fatigue, anxiety and depression and lower levels of HRQoL compared to patients with lower levels of pain who did not differ significantly from the general population in most dimensions. These results elucidate the importance of identifying patients with higher degrees of pain who are probably in need of more extensive multidimensional interventions to decrease symptom burden.

  • 30. Waldheim, E
    et al.
    Elkan, A-C
    Pettersson, S
    Vollenhoven, R van
    Bergman, S
    Frostegård, J
    Henriksson, E Welin
    Health-related quality of life, fatigue and mood in patients with SLE and high levels of pain compared to controls and patients with low levels of pain.2013In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 22, no 11, p. 1118-27Article in journal (Refereed)
    Abstract [en]

    Objective The objective of this paper is to investigate health-related quality of life (HRQoL), fatigue, anxiety and depression in patients with systemic lupus erythematosus (SLE) and higher levels of pain and to compare them to patients with lower levels of pain and controls. Method Patients were dichotomized into two groups based on SLE-related pain score on the visual analog scale (VAS): low-pain group (76%, n = 64, VAS 0-39 mm) and high-pain group (24%, n = 20, VAS 40-100 mm). Sex- and age-matched controls were randomly selected from the general population. Participants were asked to complete questionnaires regarding self-reported pain, HRQoL, fatigue, anxiety and depression. Medical assessments also were recorded. Result Fatigue score in the high-pain group (median, 36.5; interquartile range (IQR), 32.5-39.7) was significantly higher (p < 0.001) compared to the low-pain group (median, 23; IQR, 14.6-34.1), as well as scores for anxiety (median, 9; IQR, 6.5-11.5) and depression (median, 7.5; IQR, 5.5-9) (p < 0.001). The high-pain group had significantly lower scores compared to the low-pain group in all dimensions in the SF-36 (p ≤ 0.001-0.007). No statistical differences were detected between the low-pain group and controls in any measurement except for the dimensions physical function, general health, vitality and social function in SF-36. Conclusion Patients with SLE scoring higher degrees of pain were burdened with more fatigue, anxiety and depression and lower levels of HRQoL compared to patients with lower levels of pain who did not differ significantly from the general population in most dimensions. These results elucidate the importance of identifying patients with higher degrees of pain who are probably in need of more extensive multidimensional interventions to decrease symptom burden.

  • 31.
    Waldheim, Eva
    et al.
    Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden; Division of Nursing, Department of Neurobiology, Care Science and Society, Karolinska Institutet, Stockholm, Sweden.
    Elkan, Ann-Charlotte
    Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Bergman, Stefan
    Research and Development Centre, Spenshult Hospital, Sweden; Department of Rheumatology, Clinical Sciences, Lund University, Lund, Sweden.
    Frostegård, Johan
    van Vollenhoven, Ronald F
    Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Henriksson, Elisabet Welin
    Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden; Division of Nursing, Department of Neurobiology, Care Science and Society, Karolinska Institutet, Stockholm, Sweden.
    Extent and characteristics of self-reported pain in patients with systemic lupus erythematosus2013In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 22, no 2, p. 136-143Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Patients' own experiences of subjective symptoms are scarcely covered, and the objective of this study was to investigate the extent and characteristics of self-reported pain in patients with systemic lupus erythematosus (SLE).

    METHODS: This study comprised a cross-sectional design where 84 patients with SLE were asked to complete self-assessments: visual analogue scale of pain and the Short-Form McGill Pain Questionnaire. Medical assessments, including ESR, SLAM, SLEDAI, and SLICC, were also performed.

    RESULTS: Of the study population, 24% reported higher levels of SLE-related pain (≥40 mm on VAS). This group had a significantly shorter disease duration, higher ESR, and higher disease activity, according to the SLAM and SLEDAI, compared to the rest of the study population. This group mainly used the words "tender," "aching," and "burning" to describe moderate and severe pain, and they used a greater number of words to describe their pain. Of the patients with higher levels of pain, 70% reported their present pain as "distressing." The most common pain location for the whole patient population was the joints. Patients rated their disease activity significantly higher than physicians did.

    CONCLUSION: These findings expand the current knowledge of the extent of SLE-related pain and how patients perceive this pain. The results can contribute to affirmative, supportive and caring communication and especially highlight SLE-related pain in patients with a short disease duration and high disease activity.

  • 32.
    Waldheim, Eva
    et al.
    Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden; Division of Nursing, Department of Neurobiology, Care Science and Society, Karolinska Institutet, Stockholm, Sweden.
    Elkan, Ann-Charlotte
    Innovation and Development SRQ (Swedish Rheumatology Quality Register), Dept. of Rheumatology, Karolinska University Hospital, Stockholm, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Pettersson, Susanne
    Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden; Division of Nursing, Department of Neurobiology, Care Science and Society, Karolinska Institutet, Stockholm, Sweden.
    van Vollenhoven, Ronald F.
    Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Bergman, Stefan
    Research and Development Centre, Spenshult Hospital, Sweden; Department of Rheumatology, Clinical Sciences, Lund University, Lund, Sweden.
    Frostegård, Johan
    Institute of Environmental Medicine, Unit of Immunology and Chronic Disease, Karolinska Institutet, Stockholm, Sweden.
    Henriksson, Elisabet Welin
    Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden; Division of Nursing, Department of Neurobiology, Care Science and Society, Karolinska Institutet, Stockholm, Sweden.
    Health-related quality of life, fatigue and mood in patients with SLE and high levels of pain compared to controls and patients with low levels of pain2013In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 22, no 11, p. 1118-1127Article in journal (Refereed)
    Abstract [en]

    Objective: The objective of this paper is to investigate health-related quality of life (HRQoL), fatigue, anxiety and depression in patients with systemic lupus erythematosus (SLE) and higher levels of pain and to compare them to patients with lower levels of pain and controls.

    Method: Patients were dichotomized into two groups based on SLE-related pain score on the visual analog scale (VAS): low-pain group (76%, n=64, VAS 0-39 mm) and high-pain group (24%, n=20, VAS 40-100 mm). Sex- and age-matched controls were randomly selected from the general population. Participants were asked to complete questionnaires regarding self-reported pain, HRQoL, fatigue, anxiety and depression. Medical assessments also were recorded.

    Result: Fatigue score in the high-pain group (median, 36.5; interquartile range (IQR), 32.5-39.7) was significantly higher (p<0.001) compared to the low-pain group (median, 23; IQR, 14.6-34.1), as well as scores for anxiety (median, 9; IQR, 6.5-11.5) and depression (median, 7.5; IQR, 5.5-9) (p<0.001). The high-pain group had significantly lower scores compared to the low-pain group in all dimensions in the SF-36 (p ≤ 0.001-0.007). No statistical differences were detected between the low-pain group and controls in any measurement except for the dimensions physical function, general health, vitality and social function in SF-36. Conclusion Patients with SLE scoring higher degrees of pain were burdened with more fatigue, anxiety and depression and lower levels of HRQoL compared to patients with lower levels of pain who did not differ significantly from the general population in most dimensions. These results elucidate the importance of identifying patients with higher degrees of pain who are probably in need of more extensive multidimensional interventions to decrease symptom burden.

  • 33.
    Åhlin, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Mathsson, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jonsdottir, Thorunn
    Unit of Rheumatology, Department of Medicine, Karolinska Institutet.
    Gunnarsson, Iva
    Unit of Rheumatology, Department of Medicine, Karolinska Institutet.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Autoantibodies associated with RNA are more enriched than anti-dsDNA antibodies in circulating immune complexes in SLE2012In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 21, no 6, p. 586-595Article in journal (Refereed)
    Abstract [en]

    To what extent different autoantibodies accumulate in systemic lupus erythematosus (SLE) immune complexes (ICs), and whether such accumulation is associated with disease activity has been investigated. ICs were isolated from SLE sera by both polyethylene glycol (PEG) precipitation and C1q-binding. Autoantibody specificities were determined using a lineblot assay quantified by densitometry. To compare the relative levels of autoantibodies, levels were normalized to the total levels of IgG measured by ELISA in sera and parallel ICs. Samples were investigated both in a cross-sectional design as well as in a paired design with samples obtained during both active and inactive SLE. All investigated autoantibody specificities except anti-dsDNA were enriched in circulating ICs as compared with parallel sera. The group of antibodies against RNA-associated antigens (anti-RNP/Sm, anti-Sm, anti-SSA/Ro60, anti-SSA/Ro52, anti-SSB/La) all exhibited higher median enrichment than the DNA-associated (anti-dsDNA, anti-histones, anti-nucleosomes) or cytoplasmic (anti-ribosomal P) antigens. In particular autoantibodies against RNP/Sm and SSA/Ro52 had the highest degree of enrichment in SLE PEG precipitates. These findings were corroborated by analysis of autoantibody content in C1q-bound ICs. There was no difference in degree of IC accumulation of the investigated autoantibodies during active and inactive SLE. Our findings demonstrate a difference in enrichment between autoantibodies against RNA- and DNA-associated autoantigens in isolated SLE IC, suggesting that the RNA-associated autoantibodies are more prone to form circulating ICs in SLE, in contrast to antibodies against DNA-associated autoantigens such as dsDNA. These finding have implications in understanding mechanisms of differential autoantibody accumulation in target organs in SLE.

1 - 33 of 33
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf