| 1. |
- Bengtsson, Anders A., et al.
(författare)
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Neutrophil FcγRIIA availability is associated with disease activity in systemic lupus erythematosus
- 2020
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Immune complexes (ICs) are detectable in a variety of inflammatory diseases, including systemic lupus erythematosus (SLE), reflecting autoantibody binding to antigens. Though ICs are the main contributors to disease pathogenesis through FcγR-mediated inflammation and organ damage, IC levels are not part of the clinical assessment of SLE. The aim of this study was to explore the clinical utility of analyzing levels of ICs in SLE patients using a novel technology, IC-FLOW. Methods: Paired serum samples, at the time point of high and low disease activity (n = 92), were analyzed using two assays: an IC ELISA from a commercial company and a novel in-house flow cytometry-based method, IC-FLOW. IC-FLOW measures FcγRIIA availability on the neutrophil cell surface by flow cytometry, whereas the commercial ELISA measures IC binding to C1q. Results: Using IC-FLOW, 90% of SLE patients with active disease had elevated levels of circulating ICs (p < 0.0001). Using the commercial assay, only 17% of SLE patients had elevated levels of circulating ICs. For both assays, levels of ICs reflected active disease as determined by SLEDAI (r = 0.45, p < 0.0001) and were associated with type I IFN activity (r = 0.37, p = 0.001), and complement consumption (p = 0.0002). Levels of ICs measured with IC-FLOW, but not with the commercial ELISA, were associated with active lupus nephritis (p = 0.004). Conclusions: This novel FcγRIIA-IC assay can detect levels of circulating ICs in patients with SLE. Analyzing IC levels may facilitate monitoring of disease activity, as well as identify patients at risk of lupus nephritis, allowing for early preventive interventions.
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| 2. |
- Berthold, Elisabet, et al.
(författare)
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The risk of depression and anxiety is not increased in individuals with juvenile idiopathic arthritis - results from the south-Swedish juvenile idiopathic arthritis cohort
- 2022
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Ingår i: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 20:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChildren with chronic diseases are reported to have increased risk of psychiatric comorbidity. Few studies have investigated this risk in juvenile idiopathic arthritis (JIA), with conflicting results. We performed a population-based, longitudinal cohort study of the risk of depression and anxiety in south-Swedish patients with juvenile arthritis.MethodsThe south-Swedish JIA cohort (n = 640), a population-based cohort with validated JIA diagnosis 1980 – 2010 and comparators, a reference group of 3200 individuals free from JIA, matched for sex, year of birth and residential region, was used. Data on comorbid diagnosis with depression or anxiety were obtained from the Skåne Healthcare Register, containing all healthcare contacts in the region, from 1998 to 2019. We used Cox proportional models for the calculation of hazard ratios.ResultsDuring the study period, 1998 to 2019, 93 (14.5%) of the individuals in the JIA group were diagnosed with depression, and 111 (17.3%) with anxiety. Corresponding numbers among the references was 474 (14.8%) with depression and 557 (17.4%) with anxiety. Hazard ratio for depression was 1.1 (95% CI 0.9 – 1.5) in females and 0.8 (95% CI 0.5 – 1.4) in males, and for anxiety 1.2 (95% CI 0.9 – 1.5) in females and 0.6 (95% CI 0.4 – 1.1) in males. There were no statistically significant hazard ratios when analyzing subgroups of JIA patients with long disease duration or treatment with disease-modifying antirheumatic drugs.ConclusionsIndividuals with JIA do not have any statistically increased risk of being diagnosed with depression or anxiety compared to matched references.
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| 3. |
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| 4. |
- Ehrsson, Ylva Tiblom, et al.
(författare)
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Self-reported sexually transmitted infections among female university students.
- 2016
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 121:1, s. 45-49
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate the occurrence of self-reported sexually transmitted infections (STIs) and associated factors among female university students requesting contraceptive counselling.MATERIAL AND METHODS: Cross-sectional study. Female university students (n = 353) completed a waiting-room questionnaire in connection with contraceptive counselling at a Student Health Centre in Uppsala, Sweden.RESULTS: Ninety-three (26.3%) female students had experienced an STI. The three most frequently reported STIs were chlamydia trachomatis, condyloma, and genital herpes. The experience of an STI was significantly associated with the total number of sexual partners (OR 1.060, 95% CI 1.030-1.091, P < 0.001), being heterosexual (OR 4.640, 95% CI 1.321-16.290, P = 0.017), having experienced an abortion (OR 2.744, 95% CI 1.112-6.771, P = 0.028), not being HPV-vaccinated (OR 2.696, 95% CI 1.473-4.935, P = 0.001), and having had intercourse on first night without using a condom (OR 2.375, 95% CI 1.182-4.771, P = 0.015).CONCLUSIONS: Contraceptive counselling should also include information about primary and secondary prevention of STI, such as the importance of correct use of a condom and STI testing, to prevent a further spread of STIs.
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| 5. |
- Gullstrand, Birgitta, et al.
(författare)
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Combination of Autoantibodies Against Different Histone Proteins Influences Complement-dependent Phagocytosis of Necrotic Cell Material by Polymorphonuclear Leukocytes in Systemic Lupus Erythematosus.
- 2012
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 39:8, s. 1619-1627
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Polymorphonuclear leukocytes (PMN) with autoantibody-coated engulfed necrotic cell material (NC) are frequently seen in systemic lupus erythematosus (SLE). We evaluated the roles of complement, different antihistone antibodies (anti-H ab), and oxidative burst in the phagocytosis of NC by PMN, as well as association to disease activity and clinical phenotype in SLE. METHODS: ELISA and immunoblot were used to measure antibodies to different histone proteins in sera from patients with SLE and complement-deficient individuals. Phagocytosis of NC by PMN and oxidative burst activity was assessed by flow cytometry. RESULTS: A clearly increased phagocytosis of NC was seen in patients with active SLE, which was associated with high levels of anti-H ab concentrations and oxidative burst activity. The complement system contributed to efficient phagocytosis of NC by PMN through activation of the classical pathway, and the phagocytosis was mediated by FcγRIIA, FcγRIIIB, and CR1 in combination. A pattern of high phagocytosis, consumption of classical pathway components, and a broad anti-H ab repertoire was seen particularly in patients with nephritis and serositis. The combination of antibodies to several different histone proteins, often with anti-DNA antibodies, promoted an efficient uptake of NC, whereas antibodies against only histone H1 or a few histones seemed to be of less importance. CONCLUSION: The distributions of specificities among anti-H ab are of great importance in the complement-dependent phagocytosis of debris from NC in SLE. Measurement of anti-H ab could be useful in monitoring of this disease and contribute to improved understanding of the autoimmune process.
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| 6. |
- Han, Bobby Kwanghoon, et al.
(författare)
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Neutrophil and lymphocyte counts are associated with different immunopathological mechanisms in systemic lupus erythematosus
- 2020
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Ingår i: Lupus Science and Medicine. - : BMJ. - 2053-8790. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Neutrophils contribute to the SLE pathogenesis. Neutrophil to lymphocyte ratio (NLR) is reported to correlate with disease activity in SLE. The aim of the study was to evaluate whether NLR reflects underlying immunopathogenic activity in SLE, as well as to determine the contribution of each component of NLR, neutrophil and lymphocyte count. Methods: Data were obtained from a cohort of patients with SLE (n=141) recruited at Lund University, Sweden. NLR levels were compared between patients with SLE and healthy controls (n=79). The relationship between NLR and clinical and immunological markers was examined using Mann-Whitney U test and logistic regression analysis. High NLR was defined as above the 90th percentile of healthy individuals. Results: Patients with SLE had elevated neutrophil count (p=0.04) and reduced lymphocyte count (p<0.0001), resulting in elevated NLR as compared with healthy controls (p<0.0001). Patients with high NLR had more active disease, and were more frequently on prednisone use and immunosuppressive medicines. High NLR was associated with immune complex (IC)-driven disease with presence of antidouble-stranded DNA antibodies (p=0.006), circulating ICs (p=0.02) and type I interferon (IFN) activity (p=0.009). Further, high NLR was associated with neutrophil abnormalities, including enrichment for low-density granulocytes (LDGs) (p=0.001), and increased levels of the serum neutrophil activation marker, calprotectin (p=0.02). Assessing the individual components within NLR, that is, neutrophil and lymphocyte count, high neutrophil count was associated with neutrophil activation markers (p<0.0001), whereas low lymphocyte count was associated with type I IFN activity and elevated numbers of LDGs (p=0.006 and p=0.001, respectively). Conclusions: NLR is elevated in patients with SLE as compared with healthy individuals, and is associated with key immunopathological events, including type I IFN activity and neutrophil activation. Neutrophil and lymphocyte count reflected different aspects of the pathogenesis of SLE. Further studies are needed to determine the causality of the associations.
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| 7. |
- Leffler, Jonatan, et al.
(författare)
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Neutrophil Extracellular Traps That Are Not Degraded in Systemic Lupus Erythematosus Activate Complement Exacerbating the Disease.
- 2012
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Ingår i: Journal of immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 188:7, s. 3522-3531
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Tidskriftsartikel (refereegranskat)abstract
- Ongoing inflammation including activation of the complement system is a hallmark of systemic lupus erythematosus (SLE). Antimicrobial neutrophil extracellular traps (NETs) are composed of secreted chromatin that may act as a source of autoantigens typical for SLE. In this study, we investigated how complement interacts with NETs and how NET degradation is affected by complement in SLE patients. We found that sera from a subset of patients with active SLE had a reduced ability to degrade in vitro-generated NETs, which was mostly restored when these patients were in remission. Patients that failed to degrade NETs had a more active disease and they also displayed lower levels of complement proteins C4 and C3 in blood. We discovered that NETs activated complement in vitro and that deposited C1q inhibited NET degradation including a direct inhibition of DNase-I by C1q. Complement deposition on NETs may facilitate autoantibody production, and indeed, Abs against NETs and NET epitopes were more pronounced in patients with impaired ability to degrade NETs. NET-bound autoantibodies inhibited degradation but also further increased C1q deposition, potentially exacerbating the disease. Thus, NETs are a potent complement activator, and this interaction may play an important role in SLE. Targeting complement with inhibitors or by removing complement activators such as NETs could be beneficial for patients with SLE.
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| 8. |
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| 9. |
- Linge, Carl Petrus, et al.
(författare)
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Enrichment of Complement, Immunoglobulins, and Autoantibody Targets in the Proteome of Platelets from Patients with Systemic Lupus Erythematosus
- 2022
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 122:9, s. 1486-1501
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Tidskriftsartikel (refereegranskat)abstract
- Background Systemic lupus erythematosus (SLE) is a complex disease characterized by autoimmunity toward apoptotic cells, excessive amounts of circulating immune complexes, and complement activation. A decreased platelet size has been observed in SLE and their nonhemostatic functions may play an active role in the disease. The main objective of this study was to find clues that could explain their decreased size and functional role, analyzing the entire platelet proteome. Methods Platelets were isolated from 23 patients with SLE. The five individuals with the highest and lowest average platelet forward scatter were selected for further analysis. Platelet protein content was analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) and compared with platelets from five healthy controls. Data are available via ProteomeXchange with identifier PXD031202. Results Out of 2,572 proteins identified, 396 had significantly different levels (ANOVA q-value ≤ 0.01). Forty proteins, including immunoglobulin-, complement- and phosphatidylserinebinding proteins had higher abundance in platelets from SLE patients, largely independent of size (fold difference of ≥1.5 and a t-test p-value of ≤0.05 as cut-off). Functional characterization revealed increased degranulation and skewed hemostatic balance in platelets from SLE patients. In the SLE proteome, immunoglobulin proteins were negatively correlated to serum complement C3 and C4 and the highest relative levels were detected in platelets of normal size. Conclusion Platelets from SLE patients shared a specific protein profile, including immunoglobulins, complement proteins, and autoantigens, largely independent of the platelet size and in agreement with an integrated role for platelets in SLE.
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| 10. |
- Linge, Petrus, et al.
(författare)
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NCF1-339 polymorphism is associated with altered formation of neutrophil extracellular traps, high serum interferon activity and antiphospholipid syndrome in systemic lupus erythematosus
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 79:2, s. 254-261
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: A single nucleotide polymorphism in the NCF1 gene (NCF1-339, rs201802880), encoding NADPH oxidase type II subunit NCF1/p47phox, reducing production of reactive oxygen species (ROS) is strongly associated with the development of systemic lupus erythematosus (SLE). This study aimed at characterising NCF1-339 effects on neutrophil extracellular trap (NET) formation, type I interferon activity and antibody profile in patients with SLE. Methods: Neutrophil NET-release pathways (n=31), serum interferon (n=141) and finally antibody profiles (n=305) were investigated in SLE subjects from Lund, genotyped for NCF1-339. Then, 1087 SLE subjects from the rheumatology departments of four Swedish SLE centres, genotyped for NCF1-339, were clinically characterised to validate these findings. Results: Compared with patients with normal-ROS NCF1-339 genotypes, neutrophils from patients with SLE with low-ROS NCF1-339 genotypes displayed impaired NET formation (p<0.01) and increased dependence on mitochondrial ROS (p<0.05). Low-ROS patients also had increased frequency of high serum interferon activity (80% vs 21.4%, p<0.05) and positivity for anti-β2 glycoprotein I (p<0.01) and anticardiolipin antibodies (p<0.05) but were not associated with other antibodies. We confirmed an over-representation of having any antiphospholipid antibody, OR 1.40 (95% CI 1.01 to 1.95), anti-β2 glycoprotein I, OR 1.82 (95% CI 1.02 to 3.24) and the antiphospholipid syndrome (APS), OR 1.74 (95% CI 1.19 to 2.55) in all four cohorts (n=1087). Conclusions: The NCF1-339 SNP mediated decreased NADPH oxidase function, is associated with high interferon activity and impaired formation of NETs in SLE, allowing dependence on mitochondrial ROS. Unexpectedly, we revealed a striking connection between the ROS deficient NCF1-339 genotypes and the presence of phospholipid antibodies and APS.
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| 11. |
- Lood, Christian, et al.
(författare)
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Decreased platelet size is associated with platelet activation and anti-phospholipid syndrome in systemic lupus erythematosus
- 2017
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 56:3, s. 408-416
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: . SLE is an autoimmune disease with increased cardiovascular morbidity and platelet activation. In the general population, increased platelet size predicts platelet reactivity and cardiovascular disease. The aim of this study was to investigate whether platelet size related to platelet activation and cardiovascular disease in SLE.Methods: . Fresh blood samples from SLE patients ( n = 148), healthy volunteers ( n = 79) and disease controls ( n = 40) were analysed for platelet size and activation by flow cytometry, ELISA and cell count. Associations to manifest cardiovascular disease, venous thrombosis and APS were adjusted for traditional cardiovascular risk factors using logistic regression analysis.Results: . SLE patients had decreased platelet size as compared with healthy controls ( P = 0.003). In SLE, decreased platelet size was related to increased platelet activation, in particular microparticle formation ( P < 0.0001, r = -0.46) and release of serotonin from dense granules ( P < 0.001, r = 0.57). SLE patients with aCL had decreased platelet size ( P = 0.02) and aCL decreased platelet size in vitro ( P = 0.007). In contrast to the general population, increased platelet size was not associated with cardiovascular disease. Instead, decreased platelet size was associated with secondary APS, even after adjusting for traditional cardiovascular risk factors ( P = 0.01, odds ratio 3.58).Conclusion: . Platelet size is decreased in SLE patients and associated with microparticle formation and APS. Future studies are needed to determine the underlying mechanism(s) as well as the potential predictive value of small platelets for disease complications in SLE.
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| 12. |
- Lood, Christian, et al.
(författare)
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Platelet activation and anti-phospholipid antibodies collaborate in the activation of the complement system on platelets in systemic lupus erythematosus.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Anti-phospholipid (aPL) antibodies are important contributors to development of thrombosis in patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE). The underlying mechanism of aPL antibody-mediated thrombosis is not fully understood but existing data suggest that platelets and the complement system are key components. Complement activation on platelets is seen in SLE patients, especially in patients with aPL antibodies, and has been related to venous thrombosis and stroke. The aim of this study was to investigate if aPL antibodies could support classical pathway activation on platelets in vitro as well as in SLE patients. Furthermore, we investigated if complement deposition on platelets was associated with vascular events, either arterial or venous, when the data had been adjusted for traditional cardiovascular risk factors. Finally, we analyzed if platelet complement deposition, both C1q and C4d, was specific for SLE. We found that aPL antibodies supported C4d deposition on platelets in vitro as well as in SLE patients (p = 0.001 and p<0.05, respectively). Complement deposition on platelets was increased in SLE patients when compared with healthy individuals (p<0.0001). However, high levels of C4d deposition and a pronounced C1q deposition were also seen in patients with rheumatoid arthritis and systemic sclerosis. In SLE, C4d deposition on platelets was associated with platelet activation, complement consumption, disease activity and venous (OR = 5.3, p = 0.02), but not arterial, thrombosis, observations which were independent of traditional cardiovascular risk factors. In conclusion, several mechanisms operate in SLE to amplify platelet complement deposition, of which aPL antibodies and platelet activation were identified as important contributors in this investigation. Complement deposition on platelets was identified as a marker of venous, but not arterial thrombosis, in SLE patients independently of traditional risk factors and aPL antibodies. Further studies are needed to elucidate the role of complement deposition on platelets in development of venous thrombosis.
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| 13. |
- Lood, Christian, et al.
(författare)
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Platelet-derived S100A8/A9 and cardiovascular disease in systemic lupus erythematosus.
- 2016
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5205 .- 2326-5191.
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Tidskriftsartikel (refereegranskat)abstract
- S100A8/A9, a pro-inflammatory and pro-thrombotic protein complex, is increased in several diseases and high levels predispose to cardiovascular disease (CVD). Recently, platelet S100A8/A9 synthesis was described in mouse and humans in relation to CVD. However, the role of platelet S100A8/A9 in systemic lupus erythematosus (SLE), a disease with markedly increased cardiovascular morbidity, as well as the exact platelet distribution of the S100A8/A9 proteins has not been investigated.
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| 14. |
- Lood, Christian, et al.
(författare)
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Protein synthesis of the pro-inflammatory S100A8/A9 complex in plasmacytoid dendritic cells and cell surface S100A8/A9 on leukocyte subpopulations in systemic lupus erythematosus
- 2011
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease with chronic or episodic inflammation in many different organ systems, activation of leukocytes and production of pro-inflammatory cytokines. The heterodimer of the cytosolic calcium-binding proteins S100A8 and S100A9 (S100A8/A9) is secreted by activated polymorphonuclear neutrophils (PMNs) and monocytes and serves as a serum marker for several inflammatory diseases. Furthermore, S100A8 and S100A9 have many pro-inflammatory properties such as binding to Toll-like receptor 4 (TLR4). In this study we investigated if aberrant cell surface S100A8/A9 could be seen in SLE and if plasmacytoid dendritic cells (pDCs) could synthesize S100A8/A9. Methods: Flow cytometry, confocal microscopy and real-time PCR of flow cytometry-sorted cells were used to measure cell surface S100A8/A9, intracellular S100A8/A9 and mRNA levels of S100A8 and S100A9, respectively. Results: Cell surface S100A8/A9 was detected on all leukocyte subpopulations investigated except for T cells. By confocal microscopy, real-time PCR and stimulation assays, we could demonstrate that pDCs, monocytes and PMNs could synthesize S100A8/A9. Furthermore, pDC cell surface S100A8/A9 was higher in patients with active disease as compared to patients with inactive disease. Upon immune complex stimulation, pDCs up-regulated the cell surface S100A8/A9. SLE patients had also increased serum levels of S100A8/A9. Conclusions: Patients with SLE had increased cell surface S100A8/A9, which could be important in amplification and persistence of inflammation. Importantly, pDCs were able to synthesize S100A8/A9 proteins and up-regulate the cell surface expression upon immune complex-stimulation. Thus, S100A8/A9 may be a potent target for treatment of inflammatory diseases such as SLE.
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| 15. |
- Lood, Christian, et al.
(författare)
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Type I interferon-mediated skewing of the serotonin synthesis is associated with severe disease in systemic lupus erythematosus.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Serotonin, a highly pro-inflammatory molecule released by activated platelets, is formed by tryptophan. Tryptophan is also needed in the production of kynurenine, a process mediated by the type I interferon (IFN)-regulated rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO). The aim of this study was to investigate levels of serotonin in patients with the autoimmune disease systemic lupus erythematosus (SLE), association to clinical phenotype and possible involvement of IDO in regulation of serotonin synthesis. Serotonin levels were measured in serum and plasma from patients with SLE (n=148) and healthy volunteers (n=79) by liquid chromatography and ELISA, as well as intracellularly in platelets by flow cytometry. We found that SLE patients had decreased serotonin levels in serum (p=0.01) and platelets (p<0.0001) as compared to healthy individuals. SLE patients with ongoing type I IFN activity, as determined by an in-house reporter assay, had decreased serum levels of serotonin (p=0.0008) as well as increased IDO activity (p<0.0001), as determined by the kynurenine/tryptophan ratio measured by liquid chromatography. Furthermore, SLE sera induced IDO expression in WISH cells in a type I IFN-dependent manner (p=0.008). Also platelet activation contributed to reduce overall availability of serotonin levels in platelets and serum (p<0.05). Decreased serum serotonin levels were associated with severe SLE with presence of anti-dsDNA antibodies and nephritis. In all, reduced serum serotonin levels in SLE patients were related to severe disease phenotype, including nephritis, suggesting involvement of important immunopathological processes. Further, our data suggest that type I IFNs, present in SLE sera, are able to up-regulate IDO expression, which may lead to decreased serum serotonin levels.
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| 16. |
- Moore, Stanley, et al.
(författare)
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Role of Neutrophil Extracellular Traps Regarding Patients at Risk of Increased Disease Activity and Cardiovascular Comorbidity in Systemic Lupus Erythematosus
- 2020
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Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 47:11, s. 1652-1660
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Neutrophil extracellular traps (NET) are essential in host defense, but are also linked to inflammation and autoimmunity, including in systemic lupus erythematosus (SLE). We recently described that immune complexes (IC) induce NET formation, promoting SLE-like disease in mice. In the current study, we investigated, for the first time to our knowledge, the role of NET in human SLE and their association with disease activity and severity. METHODS: Levels of NET (myeloperoxidase-DNA complexes) were analyzed in plasma from 4 cross-sectional SLE cohorts (n = 44-142), 1 longitudinal SLE cohort (n = 47), and healthy individuals (n = 100) using ELISA. Type I interferon activity was determined using a cell reporter system. RESULTS: Patients with SLE had elevated levels of NET in circulation compared to healthy controls (p < 0.01). NET levels identified patients with a severe disease phenotype characterized by IC-driven nephritis (p < 0.05). Though not associated with current disease activity (p = 0.20), levels of NET were associated with future increase in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) within 3 months (OR 1.75, p = 0.01), as well as an overall heightened SLEDAI over 1 year (p < 0.01). Finally, levels of NET were associated with arterial events (OR 5.0, p = 0.02) and endothelial cell activation (p < 0.001). CONCLUSION: NET levels are elevated in patients with SLE, associated with IC-driven disease. NET levels provide significant clinical value in identifying patients at risk of active disease and/or severe disease, including nephritis and cardiovascular disease, and may allow for early interventions.
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| 17. |
- Nived, Ola, et al.
(författare)
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Disease duration, age at diagnosis and organ damage are important factors for cardiovascular disease in SLE
- 2020
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Ingår i: Lupus science & medicine. - : BMJ. - 2053-8790. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To report the incidence rate ratios (IRR) of acute myocardial infarctions (AMI) and cerebrovascular events (CVE) in incident SLE cases from a defined population. To study the risk factors for cardiovascular events in all patients with SLE at our unit.METHODS: Patients with SLE diagnosed from 1981 to 2006 were followed through to 2016. IRRs of AMI and CVE were calculated. The AMI and CVE incidence patterns for patients with SLE were studied in relation to hypertension, smoking, renal dysfunction, anticardiolipin (aCL) antibodies at diagnosis, disease duration and organ damage before an event.RESULTS: 262 patients with SLE were included in the study; of these 175 were from the defined population. Overall, 37 AMI and 44 CVE were recorded. An increased IRR of 3 for AMI was found (p<0.001). Smoking, hypertension and reduced renal function were risk factors for AMI. An increased IRR of 3.3 for ischaemic CVE was found for women (p<0.001). Hypertension and aCL were risk factors for CVE. Organ damage before events was increased.CONCLUSIONS: Cardiovascular events are increased in SLE and are associated with hypertension, smoking and increased damage rate.
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| 18. |
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| 19. |
- Skogsdal, Yvonne, 1964-
(författare)
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Preconception health in Sweden : The impact of lifestyle factors and the role of midwife's counselling
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Preconception health is an important topic since women and men have a possibility to change lifestyle habits preceding pregnancies, to increase the chances of a healthy pregnancy and child. The aim of this thesis was to increase knowledge about fertility and awareness of preconception health. Studies I and II were based on a randomised controlled trial among women who visited midwives for contraceptives counselling. Questionnaires were used before and after an intervention with the Reproductive Life plan (RLP), which is a discussion tool for preconception health. Study I showed that women do not always use a contraceptive that is suitable for their reproductive intentions and Study II indicated that women´s knowledge about fertility and awareness of preconception health increased with RLP-counselling (RLPC). Study II also showed that women appreciated the RLPC by the midwives.In studies III and IV, data from the Swedish Pregnancy Register were used. The main findings in Study III were that smoking, and use of snuff, in early pregnancy and risk consuming of alcohol the year preceding pregnancy were associated with spontaneous abortion (SA). Study IV showed that heavy alcohol consumption the year preceding pregnancy was associated with lower Apgar-score and might have been associated with lower birth weight. The studies contribute important new knowledge about lifestyle factors preceding pregnancy. It is important to highlight this new knowledge together with other factors about preconception health to midwives and other healthcare providers. Preconception counselling is also needed to increase women´s (and men´s) knowledge. There is still a lack of knowledge in the field, but it is a golden opportunity for midwives to start talking about reproductive health during contraception counselling.
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| 20. |
- Skogsdal, Yvonne Rosalie Elisabeth, 1964-, et al.
(författare)
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An intervention in contraceptive counseling increased the knowledge about fertility and awareness of preconception health-a randomized controlled trial
- 2019
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Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis. - 0300-9734 .- 2000-1967. ; 124:3, s. 203-212
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reproductive life plan counseling (RLPC) is a tool to encourage women and men to reflect upon their reproduction, to avoid unintended pregnancies and negative health behavior that can threaten reproduction. The aim was to evaluate the effect of RLPC among women attending contraceptive counseling. Outcomes were knowledge about fertility and awareness of preconception health, use of contraception, and women's experience of RLPC.Material and methods: Swedish-speaking women, aged 20-40 years, were randomized to intervention group (IG) or control group (CG). Participants (n = 1,946) answered a questionnaire before and two months after (n = 1,198, 62%) the consultation. All women received standard contraceptive counseling, and the IG also received the RLPC, i.e. questions on reproductive intentions, information about fertility, and preconception health.Results: Women in the IG increased their knowledge about fertility: age and fertility, chances of getting pregnant, fecundity of an ovum, and chances of having a child with help of IVF. They also increased their awareness of factors affecting preconception health, such as to stop using tobacco, to refrain from alcohol, to be of normal weight, and to start with folic acid before a pregnancy. The most commonly used contraceptive method was combined oral contraceptives, followed by long-acting reversible contraception. Three out of four women (76%) in the IG stated that the RLPC should be part of the routine in contraceptive counseling.Conclusions: Knowledge about fertility and awareness of preconception health increased after the intervention. The RLPC can be recommended as a tool in contraceptive counseling.
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| 21. |
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| 22. |
- Skogsdal, Yvonne Rosalie Elisabeth, 1964-, et al.
(författare)
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Contraceptive use and reproductive intentions among women requesting contraceptive counseling
- 2018
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 97:11, s. 1349-1357
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Limited attention has been paid to the use of contraception in relation to women's family planning intentions. The aim of this study was to investigate the use of contraception during the most recent intercourse as well as the reproductive intentions of Swedish-speaking women requesting contraceptive counseling.Material and methods: Across-sectional baseline survey in a randomized controlled trial regarding reproductive life planning (before randomization). Women requesting contraceptive counseling answered questions about contraception and whether they wanted to have children/more children in the future.Results: In total, 1946 women participated: 33.7% (n = 656) parous and 65.7% (n = 1279) nulliparous. The majority, 87.1% (n = 1682), had used contraception during their latest intercourse; 64.6% (n = 1239) used short-acting reversible contraception, 22.8% (n = 443) used long-acting reversible contraception (LARC), and 12.9% (n = 251) had not used any contraception. A combined oral contraceptive was more common among nulliparous and LARC among parous. Among all women, 64.8% (n = 1253) intended to have children/more children in the future, among parous women 35.7% (n = 220) and among nulliparous 80.0% (n = 1033). Among women who did not intend to have children/more children, 22.6% (n = 60) of parous and 10% (n = 8) of nulliparous had not used contraceptives during their most recent intercourse.Conclusions: Women did not always use contraceptives that were suitable for their reproductive intentions. Questioning women who request contraceptive counseling about their pregnancy intention can give healthcare providers better opportunities for individualized counseling.
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| 23. |
- Skogsdal, Yvonne Rosalie Elisabeth, 1964-, et al.
(författare)
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The association of smoking, use of snuff, and preconception alcohol consumption with spontaneous abortion : A population-based cohort study
- 2023
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 102:1, s. 15-24
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionIt is unclear whether tobacco in early pregnancy and alcohol use preceding pregnancy are associated with spontaneous abortion. The purpose was to investigate if use of tobacco and/or alcohol is associated with spontaneous abortion among women attending antenatal care, and if age and body mass index (BMI) attenuate the risk.Material and MethodsA population-based cohort study based on data from the Swedish Pregnancy Register. All pregnant women having had the first antenatal visit from January 2014 to July 2018 were included (n = 525 604). The register had information about smoking and use of snuff before and in early pregnancy, as well as data on alcohol habits before pregnancy, measured by the Alcohol Use Disorders Identification Test (AUDIT), a validated questionnaire. Logistic regression analysis was used to estimate the association between lifestyle factors and spontaneous abortion, and multiple imputation was used to impute missing data.ResultsIn total, 34 867 (6.6%) pregnancies ended in a spontaneous abortion after the first visit to maternal health care. At the first maternal healthcare visit, daily smoking was reported by 24 214 (5.1%), and 6403 (1.2%) used snuff. For 19 837 (4.2%) women, a high alcohol score was reported for the year preceding pregnancy. After adjusting for potential confounders and multiple imputation, use of tobacco was associated with spontaneous abortion; smoking 1–9 cigarettes/day (adjusted odds ratio [aOR] 1.11, 95% confidence interval [CI] 1.04–1.18), smoking 10 or more cigarettes/day (aOR 1.12, 95% CI 1.–1.26), and use of snuff (aOR 1.20, 95% CI 1.06–1.37). Higher AUDIT scores were not significantly associated with spontaneous abortion (AUDIT 6–9: aOR 1.03, 95% CI 0.97–1.10 and AUDIT 10 or more: aOR 1.07, 95% CI 0.94–1.22). Increasing maternal age showed the highest risk of spontaneous abortion from the age of 35, and BMI of 30 kg/m2 or more increased the risk. There were interactions between different lifestyle factors associated with spontaneous abortion that could either increase or decrease the risk of spontaneous abortion.ConclusionsSmoking and use of snuff were associated with an increased risk of spontaneous abortion. The AUDIT scores preceding pregnancy were not associated with an increased risk of spontaneous abortion, which contradicts the results from previous studies.
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| 24. |
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| 25. |
- Stenhammar, Christina, et al.
(författare)
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Sexual and contraceptive behavior among female university students in Sweden : repeated surveys over a 25-year period
- 2015
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 94:3, s. 253-259
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo study female students' sexual and contraceptive behavior and compare these results with earlier surveys. DesignComparative, repeated cross-sectional surveys, started in 1989 and repeated every fifth year. SettingContraceptive counseling delivered at a Student Health Center in Sweden. PopulationFemale university students (n=359). MethodsMultiple-choice waiting-room questionnaire. Main outcome measuresSexual and contraceptive behavior. ResultsIn 1989, age at first intercourse was 17.6years vs. 16.7years in 2014, number of lifetime sexual partners was 4.0 vs. 12.1 in 2014, and number of sexual partners during the previous 12months was 1.0 vs. 2.8 in 2014. Condom use during first intercourse with the latest partner decreased from 49% to 41% (n=172 in 2009 vs. n=148 in 2014: p<0.001), and experience of anal sex increased from 39% to 46% (n=136 in 2009 vs. n=165 in 2014: p=0.038), and 25% (n=41 in 2014) always used a condom during anal sex. A total of 70% (n=251) made use of pornography, and 48% (n=121) considered their sexual behavior affected by pornography. Eighty-nine percent (n=291) wanted two to three children and 9% (n=33) had thought about freezing eggs for the future. The female students' knowledge about increasing age being correlated with decreased fertility varied. ConclusionsSexual behavior among female university students has gradually changed during the last 25years and behavior appears more risky today. As this may have consequences on future reproductive health, it is vital to inform women about consistent and correct condom use and about the limitations of the fertile window.
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| 26. |
- Tarbiat, Behdad, et al.
(författare)
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Effect of a targeted treatment strategy against Ascaridia galli on egg production, egg quality and bird health in a laying hen farm
- 2020
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Ingår i: Veterinary Parasitology. - : Elsevier BV. - 0304-4017 .- 1873-2550. ; 286
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Tidskriftsartikel (refereegranskat)abstract
- Worm control is an important aspect of the successful management of the egg production industry. Of particular concern is Ascaridia galli, which at high parasite loads affect health and production in layers. Application of a targeted treatment strategy (TT) to control A. galli has shown promise. The purpose of this study was to explore the effect of such a strategy on welfare indicators and production performance of layers. Six flocks (F1-6) on a commercial farm were allocated to three treatment groups. Flocks Fl and F4 were treated (TT) with fenbendazole at 22, 27 and 36 weeks post-placement (WPP). Flocks F2 and F5 were treated at 27 WPP (conventional treatment, CT) and hens in flocks F3 and F6 served as untreated (UT) control groups. At 19, 35 and 45 WPP twenty-five hens plus thirty eggs per flock were randomly selected. Hens were weighed and their plumage conditions (PC) were assessed. The eggs were subjected to various external and interior quality analyses. Production data such as number of eggs/hen/week, egg mass and feed conversion ratio (FCR) were calculated from raw data obtained from all flocks on a weekly basis. The number of eggs/hen/week, egg mass and FCR were higher (P < 0.05) in the TT flocks and hens had better PC both at 35 and 45 WPP compared with other flocks. No differences in body weight and physical egg quality were observed between groups except for egg shell strength which was higher (P < 0.05) in the CT flocks. These data suggest that better production performance and plumage, which suggests improved health, can be achieved through the application of a TT strategy. The insights gained from this research should help to justify the extra cost and labor associated with the TT strategy.
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| 27. |
- Tyden, Gunnar, et al.
(författare)
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A Randomized, Doubleblind, Placebo-Controlled, Study of Single-Dose Rituximab as Induction in Renal Transplantation
- 2009
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Ingår i: Transplantation. - 1534-6080 .- 0041-1337. ; 87:9, s. 1325-1329
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Tidskriftsartikel (refereegranskat)abstract
- We performed a prospective, double blind, randomized, placebo-controlled multicenter study on the efficacy and safety of rituximab as induction therapy, together with tacrolimus, mycophenolate mofetil, and steroids. The primary endpoint was defined as acute rejection, graft loss, or death during the first 6 months. Secondary endpoints were creatinine clearance, incidence of infections, and incidence of rituximab-related adverse event. Results. We enrolled 140 patients (44 living donor and 96 deceased donor), and of those, 68 rituximab and 68 placebo patients fulfilled the study. In all the patients receiving rituximab, there was a complete depiction of CD 19/CD20 cells, whereas there was no change in the number of CD19/CD20 cells in the placebo group. There were 10 treatment failures in the rituximab group versus 14 in the placebo group (P=0.348). There were eight rejection episodes in the rituximab group versus 12 in the placebo group (P=0.317) Creatinine clearance was 66 +/- 22 mL/min in the study group and 67 +/- 23 mL/min in the placebo group. There was no difference in the number of bacterial infections, cytomegalovirus infections, and BK virus infections or fungal infections. Conclusion. We performed a placebo-controlled study of rituximab induction in renal transplantation. There was a tendency toward fewer and milder rejections during the first 6 months in the rituximab group. Although induction with one dose of rituximab induced a complete depletion B cells, there was no increase in the incidence of infectious complications or leukopenia and it seems safe, therefore, to conduct further studies on the use of rituximab in transplantation.
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| 28. |
- Tydén, Gunnar, et al.
(författare)
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Implementation of a Protocol for ABO-incompatible kidney transplantation--a three-center experience with 60 consecutive transplantations
- 2007
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 7, s. 157-158
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Tidskriftsartikel (refereegranskat)abstract
- Background. A new protocol for ABO-incompatible kidney transplantation has recently been introduced. We report here on the joint experience of the implementation in Stockholm and Uppsala, Sweden and Freiburg, Germany. Methods. The new protocol utilizes antigen-specific immunoadsorption to remove existing ABO-antibodies, rituximab, and intravenous immunoglobulin to prevent the rebound of antibodies, and conventional tacrolimus, mycophenolate-mofetil, and prednisolone immunosuppression. Sixty consecutive ABO-incompatible kidney transplantations were included in the study. The outcome is compared with the results of 274 ABO-compatible live donor transplantations performed during the same period. Results. Two of the ABO-incompatible grafts have been lost (non-compliance and death with functioning graft). All the remaining 58 grafts had good renal function at a follow-up of up to 61 months. We did not observe any late rebound of antibodies and there were no humoral rejections. Graft survival was 97% for the ABO-incompatible compared with 95% for the ABO-compatible. Patient survival was 98% in both groups. There was a significant variation in preoperative A/B-antibody titer between the centers, with a median 1:8 in Uppsala, median 1:32 in Stockholm and median 1:128 in Freiburg. More preoperative antibody adsorptions were therefore needed in Freiburg than in Stockholm and Uppsala. Conclusions. The new protocol was easily implemented and there were no graft losses that could be related to ABO-incompatibility. A significant inter-institutional variation in the measurement of anti-AB-antibodies was found, having a substantial impact on the number of immunoadsorptions and consequently on the total cost for the procedure. A standardized fluorescence-activated cell sorting technique for antibody quantification is much needed.
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| 29. |
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| 30. |
- Tydén, Helena, et al.
(författare)
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Increased serum levels of S100A8/A9 and S100A12 are associated with cardiovascular disease in patients with inactive systemic lupus erythematosus.
- 2013
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 52:11, s. 2048-2055
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Patients with SLE have an increased morbidity and mortality from cardiovascular disease (CVD). The reason for this is not entirely understood, but is believed to be partly related to the long-lasting inflammatory process seen in SLE. The aim of the present study was to investigate whether there is an association between CVD and serum levels of the proinflammatory proteins S100A8/A9 and S100A12 in SLE.Methods. Serum levels of S100A8/A9 and S100A12 were measured with ELISA in 237 SLE patients with clinically inactive disease and without infections, as well as in 100 healthy individuals. Cardiovascular manifestations were defined according to the SLICC/ACR Damage Index (SLICC/ACR-DI).Results. Serum levels of S100A8/A9 were elevated in our inactive SLE patients as compared with healthy individuals (P < 0.0001), which was not seen for S100A12 (P = 0.12). SLE patients with a history of CVD had increased serum levels of both S100A8/A9 and S100A12 compared with patients with no CVD or venous thromboembolism (P = 0.003 and P = 0.006, respectively). The presence of organ damage according to SLICC/ACR-DI was associated with an increase in both S100A8/A9 and S100A12 serum levels (P = 0.001 and P = 0.006, respectively).Conclusion. Elevated serum levels of S100A8/A9 and S100A12 may be used as an indicator of severe disease and CVD in SLE, suggesting that SLE patients with elevated serum S100A8/A9 and S100A12 concentrations may benefit from more intense cardiovascular primary preventive strategies and possibly also from more intense and early immunosuppressive treatment.
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| 31. |
- Tydén, Helena, et al.
(författare)
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Low plasma concentrations of apolipoprotein M are associated with disease activity and endothelial dysfunction in systemic lupus erythematosus
- 2019
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Apolipoprotein M (apoM) is a 25-kDa apolipoprotein present in 5% of high-density lipoprotein (HDL) particles. It is suggested to be anti-atherogenic and to play a key role in sustaining endothelial barrier integrity. SLE patients have increased cardiovascular disease risk, and we aimed to investigate if apoM levels reflect endothelial function in SLE. Since apoM plasma levels decrease during inflammatory conditions, our aim was also to determine the impact of SLE disease activity on apoM plasma levels. Methods: Plasma concentrations of apoM were measured by ELISA in two patient groups with systemic lupus erythematosus (SLE) and in 79 healthy control individuals. In patient group I (n = 84), evaluation time points were selected with the objective to include a wide range of clinical and laboratory variables reflecting disease activity which was measured as SLEDAI. In patient group II consisting of 140 consecutive patients, endothelial function was measured by a finger plethysmograph. A low Reactive Hyperemia Index (RHI) value indicates endothelial dysfunction. Results: SLE patients had decreased levels of apoM compared to healthy controls (p < 0.01), with apoM levels correlating inversely with SLEDAI (r = - 0.31, p < 0.01) as well as with levels of CRP (r = - 0.26, p = 0.02) and positively with levels of C3 (r = 0.29, p < 0.01). ApoM levels were particularly low in patients with active disease from the kidney and skin and in patients with leukopenia or positive anti-dsDNA antibody test (p < 0.05). ApoM levels correlated with RHI values in young SLE patients (r = 0.32, p = 0.01), consistent with the important role of apoM in regulating endothelial integrity. Conclusions: ApoM levels may be regulated by SLE-related inflammatory processes and could be a marker of disease activity and endothelial dysfunction, in particular in young SLE patients. Further studies are needed to investigate the predictive value of apoM in the development of a cardiovascular disease.
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| 32. |
- Tydén, Helena, et al.
(författare)
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Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti-dsDNA antibodies in systemic lupus erythematosus
- 2017
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Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 26:2, s. 139-149
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Systemic lupus erythematosus (SLE) is associated with elevated levels of S100A8/A9, pro-inflammatory proteins mainly secreted by activated polymorphonuclear neutrophils (PMNs). The underlying mechanisms for increased S100A8/A9 levels and their relation to the clinical phenotype have not been carefully investigated. We assessed S100A8/A9 and S100A12 levels in SLE patient sera in relation to disease activity, clinical phenotype, presence of anti-dsDNA antibodies and ability to promote phagocytosis of necrotic cells (NCs) by PMNs. Methods Serum levels of S100A8/A9 and S100A12 were measured by ELISA in paired samples of 100 SLE patients at time points of higher and lower disease activity. Serum-mediated phagocytosis of NCs by PMNs was analysed by flow cytometry. Clinical data were recorded at time points of blood sampling. Results Serum levels of S100A8/A9 and S100A12 were increased in SLE patients with high disease activity compared to paired samples at low disease activity (p = 0.01 and p = 0.008, respectively). Elevated levels of S100A8/A9 were particularly seen in patients with anti-dsDNA antibodies (p = 0.01) and glomerulonephritis before treatment (p = 0.02). Immunosuppressive therapy was associated with a reduction of S100A8/A9 serum levels (p = 0.002). The ability of serum to support phagocytosis of NCs by PMNs was related to increased S100A8/A9 levels (p = 0.01). Conclusions Elevated serum levels of S100A8/A9 may be used to monitor disease activity and response to treatment in SLE patients, especially in patients with glomerulonephritis. S100A12 may be a marker of disease activity in SLE. Increased S100A8/A9 levels may reflect immune-pathological processes involving phagocytosis of immune complexes by PMNs.
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| 33. |
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| 34. |
- Wirestam, Lina, et al.
(författare)
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Low Intra-Individual Variation in Mean Platelet Volume Over Time in Systemic Lupus Erythematosus
- 2021
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Platelets have recently emerged as important immune modulators in systemic lupus erythematosus (SLE), in addition to their role in thrombosis and cardiovascular disease. However, studies investigating mean platelet volume (MPV) in SLE are often scarce, conflicting and cross-sectional. In this study, MPV was measured in clinical routine throughout a defined time-period to quantify both individual MPV fluctuations and investigate if such variations are associated with disease activity and clinical phenotypes of SLE. Of our 212 patients, 34 patients had only one MPV value reported with the remaining 178 patients having between 2 and 19 visits with recorded MPV values. The intra-individual MPV variation was low, with a median variation of 0.7 fL. This was further supported by the finding that 84% of patients stayed within their reference interval category (i.e., small, normal or large) over time. In our cohort, no correlation between disease activity and MPV neither cross-sectionally nor longitudinally was found. Mean platelet volume values were significantly smaller in SLE patients (mean 10.5 fL) compared to controls (mean 10.8 fL), p < 0.0001. Based on the reference interval, 2.4% (n = 5) of patients had large-sized platelets, 84.4% (n = 179) had normal-sized and 13.2% (n = 28) had small-sized. A larger proportion (85.7%) of patients with small-sized platelets met the anti-dsDNA criterion (ACR10b; p = 0.003) compared to patients with normal and large (57.6%) sized platelets. In conclusion, the intra-individual MPV variation was of low magnitude and fluctuations in disease activity did not have any significant impact on MPV longitudinally. This lack of variability in MPV over time indicates that measuring MPV at any time-point is sufficient. Further studies are warranted to evaluate MPV as a possible biomarker in SLE, as well as to determine the underlying mechanisms influencing platelet size in SLE.
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| 35. |
- Öhrvik, Helena, et al.
(författare)
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Cadmium Transport in a Model of Neonatal Intestinal Cells Correlates to MRP1 and Not DMT1 or FPN1
- 2013
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Ingår i: ISRN Toxicology. - : Hindawi Limited. - 2090-6188 .- 2090-6196. ; 2013, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Newborns have a higher gastrointestinal uptake of cadmium than adults. In adults, the iron transporters DMT1 and FPN1 are involved in the intestinal absorption of cadmium, while in neonates, the mechanisms for cadmium absorption are unknown. We have investigated possible cadmium transporters in the neonatal intestine by applying a model of immature human intestinal epithelial Caco-2 cells. To mimic the continuous cadmium exposure via diet in neonates, cells were allowed to differentiate for 7 days in medium containing 1 μM CdCl2. A dramatic upregulation of the MT1 gene expression followed cadmium pretreatment, indicating a high sensitivity of the immature cells to cadmium. Cadmium pretreatment increased the basolateral efflux of109Cd, without causing any effects on the passive diffusion of mannitol or the transepithelial electrical resistance. The augmented transport of cadmium was correlated to an upregulation of MRP1 gene expression and increased activity of the efflux protein MRP1. No effects were observed on gene expression of the efflux proteins MRP2 and P-gp or the iron transporters DMT1, DMT1-IRE and FPN1. In conclusion, our data indicate that continuous cadmium exposure increases the absorption of the metal in immature intestinal cells and that MRP1 is involved in the intestinal cadmium absorption in newborns.
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