| 1. |
- Alchi, B, et al.
(author)
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Autologous haematopoietic stem cell transplantation for systemic lupus erythematosus: data from the European Group for Blood and Marrow Transplantation registry
- 2013
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In: Lupus. - : SAGE Publications. - 1477-0962 .- 0961-2033. ; 22:3, s. 245-253
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Journal article (peer-reviewed)abstract
- Patients with systemic lupus erythematosus (SLE) refractory to conventional immunosuppression suffer substantial morbidity and mortality due to active disease and treatment toxicity. Immunoablation followed by autologous stem cell transplantation (ASCT) is a novel therapeutic strategy that potentially offers new hope to these patients. Methods This retrospective survey reviews the efficacy and safety of ASCT in 28 SLE patients from eight centres reported to the European Group for Blood and Marrow Transplantation (EBMT) registry between 2001 and 2008. Results Median disease duration before ASCT was 52 (nine to 396) months, 25/28 SLE patients (89%) were female, age 29 (16–48) years. At the time of ASCT, eight (one to 11) American College of Rheumatology (ACR) diagnostic criteria for SLE were present and 17 (60%) patients had nephritis. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte-colony stimulating factor in 93% of patients, and ex vivo CD34 stem cell selection was performed in 36%. Conditioning regimens were employed with either low ( n = 10) or intermediate (18) intensities. With a median follow-up of 38 (one to 110) months after ASCT, the five-year overall survival was 81 ± 8%, disease-free survival was 29 ± 9%, relapse incidence (RI) was 56 ± 11% and non-relapse mortality was 15 ± 7%. Graft manipulation by CD34+ selection was associated with a lower RI ( p = 0.001) on univariate analysis. There were five deaths within two years after ASCT: three caused by infection, one by secondary autoimmune disease and one by progressive SLE. Conclusions Our data further support the concept of immunoablation and ASCT to re-induce long-term clinical and serologic remissions in refractory SLE patients even in the absence of maintenance therapy. This study also suggests a beneficial effect of ex vivo graft manipulation on prevention of relapses post-transplantation in SLE.
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| 2. |
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| 3. |
- Anania, C, et al.
(author)
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Microcirculation as determined by iontophoresis in SLE-patients and controls
- 2012
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In: Lupus. - : SAGE Publications. - 1477-0962 .- 0961-2033. ; 21:8, s. 815-820
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Journal article (peer-reviewed)abstract
- Background: The risk of cardiovascular disease (CVD), microangiopathy and prevalence of atherosclerotic plaques are increased in Systemic Lupus Erythematosus (SLE). As systemic endothelial dysfunction is one of the earliest signs of these vascular outcomes in the general population we assessed skin microvascular endothelial function in SLE patients. Methods: Endothelial function in skin was tested with local application of acetylcholine (inducing endothelium-dependent vasodilatation) and any concomitant increase in skin perfusion was measured with Laser Doppler Fluxmetry (LDF) in 84 SLE-patients (83% women, mean age 47 years) and 81 age and sex matched controls. Common carotid intima-media thickness (cIMT) and plaque occurrence were also determined using B-mode ultrasound. Results: There were no significant differences in skin microvascular endothelial function between SLE-patients and controls. In the SLE group, endothelial function did not vary in relation to skin manifestations, Raynaud's phenomenon, nephritis or plaque occurrence. In SLE patients with CVD, however, endothelial function was impaired. Conclusion: Skin microvascular endothelial function is associated with CVD but not with early signs of atherosclerosis in SLE-patients. The endothelial function is not different in SLE-patients as compared to controls.
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| 4. |
- Arkema, EV, et al.
(author)
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Perinatal risk factors for future SLE: a population-based nested case-control study
- 2015
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In: Lupus. - : SAGE Publications. - 1477-0962 .- 0961-2033. ; 24:8, s. 869-874
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Journal article (peer-reviewed)abstract
- To investigate the association between perinatal characteristics and the offspring’s risk of lupus using population-based registers in Sweden. Methods We conducted a nested case-control study, identifying systemic lupus erythematosus (SLE) cases from the National Patient Register and controls sampled from the general population matched on birth year, sex, and residential county. We obtained data on the mother’s health and age during pregnancy and characteristics of labor and delivery from the Medical Birth Register (births from 1973 through 2008) for cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression models overall and separately for males and females. Results We identified 774 cases and 3337 controls. Age at which SLE was first observed ranged from 0 to 36 years old. High birth weight was not a risk factor for SLE and did not differ by sex. Males had a 2.4-fold increased odds of SLE if born preterm (<37 weeks; OR = 2.41; 95% CI 1.09, 5.36). Birth order was significantly associated with SLE, particularly among females (first born vs. not OR = 0.77, 95% CI 0.64, 0.94; continuous birth order OR = 1.12. 95% CI 1.02, 1.24). Conclusion Being born first was associated with reduced odds of SLE and the odds of SLE increased by 12% for every additional birth. Preterm birth was associated with increased odds in males only. Unlike previous work, high birth weight was not a risk factor for SLE.
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| 5. |
- Barkauskaite, V, et al.
(author)
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Translocation of the novel cytokine HMGB1 to the cytoplasm and extracellular space coincides with the peak of clinical activity in experimentally UV-induced lesions of cutaneous lupus erythematosus
- 2007
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In: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 16:10, s. 794-802
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Journal article (peer-reviewed)abstract
- HMGB1 is a pro-inflammatory cytokine that together with TNF-α and IL-1β is involved in the pathogenesis of spontaneously occurring skin lesions in lupus erythematosus. The purpose of the present study was to explore the sequence of events in HMGB1, TNF-α and IL-1β expression under development and resolution of experimentally induced CLE lesions. The study involved investigation of 38 serial skin biopsies acquired from photoprovoked skin lesions of nine CLE patients, using immunohistochemical staining of tissue sections. In biopsies from the clinically most active phase of skin involvement extracellular, secreted HMGB1 and increased cytoplasmic HMGB1 were found, as compared with the late and fading lesions or non-lesional skin. Besides HMGB1, increased expression of TNF-α and IL-1β was observed in dermal infiltrates of the induced CLE lesions. These cytokines were however not upregulated in all lesions, and increased expression of IL-1β was seen predominantly in late biopsies. In conclusion, extracellular and cytoplasmic HMGB1 coincides with the clinically most active phase of photoinduced lesions of cutaneous lupus, and suggests that HMGB1 is an important factor in the inflammatory autoimmune process of CLE. HMGB1 can induce expression of TNF-α and IL-1β, and formation of a pro-inflammatory loop between HMGB1, TNF-α, and IL-1β may be responsible for the prolonged and sustained inflammation in CLE. Lupus (2007) 16, 794—802.
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| 6. |
- Bengtsson, Anders, et al.
(author)
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Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies
- 2000
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In: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 9:9, s. 664-671
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Journal article (peer-reviewed)abstract
- The objective was to investigate the relation between serum levels of interferon-alpha (IFN-alpha), the activity of an endogenous IFN-alpha inducing factor (SLE-IIF), clinical and immunological disease activity as well as serum levels of antiretroviral antibodies in SLE. Serum levels of IFN-alpha were measured in serial sera from 30 patients sampled at different stages of disease activity (SLEDAI score). The SLE-IIF activity was measured by its ability to induce IFN-alpha production in cultures of normal peripheral blood mononuclear cells. Both serum IFN-alpha and SLE-IIF increased markedly at flare in serially followed patients. The SLEDAI score, levels of anti-dsDNA antibodies and IL-10 correlated positively, and complement components Clq, C3 and leukocytes correlated inversely with serum concentrations of IFN-alpha. The extent of multiple organ involvement correlated with serum IFN-alpha. No relation between concentrations of retroviral peptide binding antibodies and IFN-alpha or SLE-IIF activity was found. The close relationship between disease activity in SLE patients and IFN-alpha serum levels suggests that activation of the type 1 IFN system might be of importance in the disease process.
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| 7. |
- Bengtsson, A, et al.
(author)
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Factor V:Q506 mutation and anticardiolipin antibodies in systemic lupus erythematosus
- 1996
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In: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 5:6, s. 598-601
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Journal article (peer-reviewed)abstract
- Inherited resistance to activated protein C (APC resistance) is an important risk factor of venous thrombosis. It is caused by a point mutation in the gene coding for coagulation factor V, called FV:Q506. Arterio-venous thrombosis is a common and serious medical problem in patients with systemic lupus erythematosus (SLE). We studied the prevalence of the factor V mutation associated with APC resistance and IgG anticardiolipin antibodies (aCLs) in an epidemiological cohort of 78 Swedish SLE patients, to determine their roles as risk factors for thrombosis. In addition, a detailed evaluation of the clinical manifestations in these patients was performed. Totally, 19 (24%) of the 78 SLE patients had thrombosis, 11 (14%) had venous thrombosis and 8 (10%) had a cerebral infarction caused by occlusion of cerebral vessels. Twenty-six (33%) SLE patients were aCL positive and 8 (10%) were heterozygous for the factor V mutation. Only one of the patients with venous thrombosis and one of the patients with cerebral thrombosis had the FV:Q506 mutation, whereas 3 patients with venous thrombosis and 5 patients with cerebral infarction were aCL positive. Eleven of 19 patients with heart valve disease were aCL positive, a statistically significant association (P = 0.01). In conclusion, we found no statistically significant association between venous thrombosis and FV:Q506 mutation or venous thrombosis and aCL positivity. There was, however, an association between heart valve disease and aCL positivity.
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| 8. |
- Bengtsson, Christine, et al.
(author)
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Cardiovascular event in systemic lupus erythematosus in northern Sweden: Incidence and predictors in a 7-year follow-up study
- 2012
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In: Lupus. - London : SAGE Publications. - 0961-2033 .- 1477-0962. ; 21:4, s. 452-459
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Journal article (peer-reviewed)abstract
- 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. Lupus (2012) 21, 452-459.
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| 9. |
- Bengtsson, Christine, et al.
(author)
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Systemic lupus erythematosus and cardiac risk factors : medical record documentation and patient adherence
- 2011
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In: Lupus. - Houndmills, Basingstoke, Hampshire : Stockton. - 0961-2033 .- 1477-0962. ; 20:10, s. 1057-1062
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Journal article (peer-reviewed)abstract
- 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.
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| 10. |
- Bentow, C., et al.
(author)
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International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies
- 2016
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In: Lupus. - : SAGE PUBLICATIONS LTD. - 0961-2033 .- 1477-0962. ; 25:8, s. 864-872
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Journal article (peer-reviewed)abstract
- 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.
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