| 1. |
- Torell, Agnes, 1993, et al.
(författare)
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Low CD4+T cell count is related to specific anti-nuclear antibodies, IFNα protein positivity and disease activity in systemic lupus erythematosus pregnancy.
- 2024
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Ingår i: Arthritis research & therapy. - : BioMed Central (BMC). - 1478-6362 .- 1478-6354. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Lymphopenia, autoantibodies and activation of the type I interferon (IFN) system are common features in systemic lupus erythematosus (SLE). We speculate whether lymphocyte subset counts are affected by pregnancy and if they relate to autoantibody profiles and/or IFNα protein in SLE pregnancy.Repeated blood samples were collected during pregnancy from 80 women with SLE and 51 healthy controls (HC). Late postpartum samples were obtained from 19 of the women with SLE. Counts of CD4+and CD8+T cells, B cells and NK cells were measured by flow cytometry. Positivity for anti-nuclear antibodies (ANA) fine specificities (double-stranded DNA [dsDNA], Smith [Sm], ribonucleoprotein [RNP], chromatin, Sjögren's syndrome antigen A [SSA] and B [SSB]) and anti-phospholipid antibodies (cardiolipin [CL] and β2 glycoprotein I [β2GPI]) was assessed with multiplexed bead assay. IFNα protein concentration was quantified with Single molecule array (Simoa) immune assay. Clinical data were retrieved from medical records.Women with SLE had lower counts of all lymphocyte subsets compared to HC throughout pregnancy, but counts did not differ during pregnancy compared to postpartum. Principal component analysis revealed that low lymphocyte subset counts differentially related to autoantibody profiles, cluster one (anti-dsDNA/anti-Sm/anti-RNP/anti-Sm/RNP/anti-chromatin), cluster two (anti-SSA/anti-SSB) and cluster three (anti-CL/anti-β2GPI), IFNα protein levels and disease activity. CD4+T cell counts were lower in women positive to all ANA fine specificities in cluster one compared to those who were negative, and B cell numbers were lower in women positive for anti-dsDNA and anti-Sm compared to negative women. Moreover, CD4+T cell and B cell counts were lower in women with moderate/high compared to no/low disease activity, and CD4+T cell count was lower in IFNα protein positive relative to negative women. Finally, CD4+T cell count was unrelated to treatment.Lymphocyte subset counts are lower in SLE compared to healthy pregnancies, which seems to be a feature of the disease per se and not affected by pregnancy. Our results also indicate that low lymphocyte subset counts relate differentially to autoantibody profiles, IFNα protein levels and disease activity, which could be due to divergent disease pathways.
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| 2. |
- Torell, Agnes, 1993, et al.
(författare)
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Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus.
- 2023
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Ingår i: Arthritis research & therapy. - : BMC. - 1478-6362 .- 1478-6354. ; 25
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Tidskriftsartikel (refereegranskat)abstract
- An increased risk of pregnancy complications is seen in women with systemic lupus erythematosus (SLE), but the specific immunopathological drivers are still unclear. Hallmarks of SLE are granulocyte activation, type I interferon (IFN) overproduction, and autoantibodies. Here we examined whether low-density granulocytes (LDG) and granulocyte activation increase during pregnancy, and related the results to IFNα protein levels, autoantibody profile, and gestational age at birth.Repeated blood samples were collected during pregnancy in trimesters one, two, and three from 69 women with SLE and 27 healthy pregnant women (HC). Nineteen of the SLE women were also sampled late postpartum. LDG proportions and granulocyte activation (CD62L shedding) were measured by flow cytometry. Plasma IFNα protein concentrations were quantified by single molecule array (Simoa) immune assay. Clinical data were obtained from medical records.Women with SLE had higher LDG proportions and increased IFNα protein levels compared to HC throughout pregnancy, but neither LDG fractions nor IFNα levels differed during pregnancy compared to postpartum in SLE. Granulocyte activation status was higher in SLE relative to HC pregnancies, and it was increased during pregnancy compared to after pregnancy in SLE. Higher LDG proportions in SLE were associated with antiphospholipid positivity but not to IFNα protein levels. Finally, higher LDG proportions in trimester three correlated independently with lower gestational age at birth in SLE.Our results suggest that SLE pregnancy results in increased peripheral granulocyte priming, and that higher LDG proportions late in pregnancy are related to shorter pregnancy duration but not to IFNα blood levels in SLE.
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| 3. |
- Bengtsson, Anna, 1973-, et al.
(författare)
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Increased knowledge makes a difference!–general practitioners’ experiences of pictorial information about subclinical atherosclerosis for primary prevention: an interview study from the VIPVIZA trial
- 2021
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Ingår i: Scandinavian Journal of Primary Health Care. - : Taylor & Francis. - 0281-3432 .- 1502-7724. ; 39:1, s. 77-84
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To explore how pictorial information on subclinical atherosclerosis affects GPs’ perception of patient cardiovascular disease (CVD) risk, their communication with patients, and GPs’ attitude to the treatment of CVD risk factors.Design, setting and subjects: Fifteen individual interviews were conducted between March 2014 and December 2016, with GPs who had received pictorial information regarding their patients’ subclinical atherosclerosis. The pictorial information was also received by the patients together with written information regarding atherosclerosis and CVD risk prior to the appointment with their GP. The interviews were recorded, transcribed and analyzed using qualitative content analysis.Results: Three categories were identified in the analysis. Increased knowledge makes a difference: When patients had more in-depth knowledge regarding atherosclerosis, the consultation became more patient-centered and moved towards shared decision making. This is real, not just a number: GPs described their risk assessment and the patient’s risk perception as more accurate with pictorial information about subclinical atherosclerosis. How to deal with the result–A passive to active approach: Some GPs acted promptly on the pictorial information while others took no action.Conclusion and implications: Pictorial information regarding patients’ subclinical atherosclerosis affected GPs’ assessment of CVD risk. The communication shifted towards shared decision-making although the GPs’ attitude to the result and treatment of CVD risk factors varied. Informing patients about examination results, both in writing and pictures, prior to a consultation can facilitate shared decision making and enhance preventive measures.Trial registration: https://clinicaltrials.gov/ct2/show/NCT01849575.KEY POINTS: Providing pictorial information about carotid ultrasound results and information regarding atherosclerosis to GPs and patients affects primary prevention:Informing patients about examination results prior to a consultation can be useful in clinical practice to enhance preventive measuresGPs experienced that increased patient knowledge resulted in a more patient-centered consultation and improved shared decision-makingGPs described their risk assessment and patients’ risk perception as more accurate with pictorial information about subclinical atherosclerosis.
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| 4. |
- Bengtsson, Anna, 1973-, et al.
(författare)
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Multi-view carotid ultrasound is stronger associated with cardiovascular risk factors than presence of plaque or single carotid intima media thickness measurements in subclinical atherosclerosis
- 2023
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Ingår i: The International Journal of Cardiovascular Imaging. - : Springer Nature. - 1569-5794 .- 1875-8312. ; 39:8, s. 1461-1471
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to explore the prevalence of atherosclerosis by using multi-view ultrasound examination of the carotid arteries and its association with clinical risk factors in a middle-aged population at low to intermediate risk of cardiovascular disease (CVD). Carotid vascular ultrasound was performed in 3532 participants in the VIPVIZA trial. Mean and maximal carotid intima media thickness (cIMT) at prespecified angles and plaque presence were examined on the left and right side. Associations between CVD risk factors and ultrasound variables were quantified by partial least squares (PLS) regression. A combined ultrasound variable was computed using weights of the first PLS component. Associations between CVD risk factors and the combined multi-view ultrasound variable, single cIMT and plaque measurements, respectively, were determined using linear regression modelling. The participants’ mean age was 55.7 years and 52.9% were women. Plaque prevalence was 51.1% in men and 39.0% in women. cIMT was higher in men than in women and in the left compared with the right carotid artery. The strongest association of CVD risk factors was observed with the combined multi-view ultrasound variable (R2 = 24%), compared with single cIMT variables (R2 = 14–18%) and plaque presence (R2 = 15%). The pattern was similar in both sexes. The association with CVD risk factors and the combined ultrasound variable was stronger in 40-year olds (R2 = 22%) compared with 50- or 60-year olds (R = 12%). CVD risk factors are stronger associated with a combined ultrasound variable than plaque presence or single cIMT measures suggesting that carotid multi-view ultrasonography better captures the focality of early atherosclerosis. Clinical Trial Registration: ClinicalTrials.gov, number NCT01849575. May 8, 2013.
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| 5. |
- Bengtsson, Anna, 1973-
(författare)
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Pictorial presentation of subclinical atherosclerosis : a measure to reduce the risk for cardiovascular disease
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim was improved cardiovascular disease (CVD) prevention through the VIPVIZA intervention. This includes the provision of pictorial information of subclinical atherosclerosis to participants and their general practitioners (GPs), follow-up phone call, and written information to the participant. VIPVIZA is a Prospective Randomized Open Blinded End-point (PROBE) trial nested within VIP, a CVD prevention program in primary health care in Västerbotten county, Sweden. Middle-aged individuals at low/intermediate CVD risk were enrolled to VIPVIZA and randomized 1:1 to an intervention (n=1749) or control group (n=1783 who received no pictorial or other information). Preventive measures were managed within primary health care.At baseline, clinical risk factors were measured and carotid ultrasound examination was performed. The prevalence of subclinical atherosclerotic disease was assessed as intima media thickness and presence of plaque. The association between clinical risk factors and measures of subclinical atherosclerosis was investigated. In addition to conventional risk factor-based risk evaluation, the impact of the VIPVIZA intervention on CVD risk, traditional risk factors and pharmacological treatment was evaluated after 1 and 3 years. Individual interviews were conducted with 15 GPs to explore how a pictorial representation of subclinical atherosclerosis affects physicians in their perception and communication of CVD risk. The interviews were analyzed by qualitative content analysis.The plaque prevalence was 44.7% in this population. Clinical risk factors explained more of the variation in a combined ultrasound measurement than single measurements. The results up to three years showed a VIPVIZA intervention effect, with lower and sustained CVD risk in the intervention as compared to the control group. The effect was partly mediated by differences in intake of lipid-lowering medication and partly by lifestyle behaviour. The GPs described their risk assessment and patients’ risk perception as more accurate with the VIPVIZA intervention. Informing patients about examination results prior to a consultation can facilitate shared decision-making and enhance adherence to preventive measures.The results show that the VIPVIZA intervention reduces CVD risk over three years. In the long run this has the potential to reduce the incidence of CVD events.
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| 6. |
- Bengtsson, Anna, 1973-, et al.
(författare)
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The beneficial effect over 3 years by pictorial information to patients and their physician about subclinical atherosclerosis and cardiovascular risk : results from the VIPVIZA randomized clinical trial
- 2021
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Ingår i: American Journal of Preventive Cardiology. - : Elsevier. - 2666-6677. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Non-adherence to guidelines and preventive measures is a major challenge, particularly so to ob- tain long-term adherence to lifestyle changes and recommended medication. The objective was to investigate if pictorial information regarding subclinical carotid atherosclerosis provided to individuals and physicians gave sustained effects on cardiovascular risk beyond the previously reported effect after 1 year and up to 3 years. Methods: A Prospective Randomized Open Blinded End-point (PROBE) trial. Within a CVD prevention program in Västerbotten County, Sweden, 3532 healthy individuals aged 40, 50 or 60 years were enrolled and 1:1 ran- domized to intervention ( n = 1749; pictorial information with additional prevention materials to participants and physicians) or control group ( n = 1783; no pictorial information to participants and physicians). Preventive measures were managed within primary care. Participants were investigated at baseline during 2013–2016 and at follow-up after 1 and 3 years. Results: A beneficial effect on cardiovascular risk was observed at 3-year follow-up; Framingham Risk Score (FRS) was 13.38 for the intervention group and 14.08 for the control group ( p = 0.047) and SCORE was 1.69 vs. 1.82 ( p = 0.022). The effect observed at 1-year was sustained over 3 years after adjustment for sex and education and more pronounced among participants with a severe atherosclerotic picture at baseline.Conclusions: This study provides evidence of sustained beneficial effects on the adherence to prevention guidelines over 3 years of pictorial information about subclinical carotid atherosclerosis, resulting in lower cardiovascular risk regardless of sex and educational level. Direct visualization of the underlying still subclinical atherosclerotic disease, rather than just indirect information about risk factors and statistical risk of future myocardial infarction, stroke and death, is one way to tackle the problem of non-adherence to prevention of cardiovascular diseases.
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| 7. |
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| 8. |
- Bengtsson, Karin, 1980, et al.
(författare)
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Incidence of extra-articular manifestations in ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis : Results from a national register-based cohort study
- 2021
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Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 60:6, s. 2725-2734
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To estimate the incidence and strength of association of extra-articular manifestations [EAMs, here: anterior uveitis (AU), IBD and psoriasis] in patients with AS, undifferentiated SpA (uSpA) and PsA, compared with controls. Methods: Three mutually exclusive cohorts of patients aged 18-69 years with AS (n = 8517), uSpA (n = 10 245) and PsA (n = 22 667) were identified in the Swedish National Patient Register 2001-2015. Age-, sex- and geography-matched controls were identified from the Swedish Population Register. Follow-up began 1 January 2006, or six months after the first SpA diagnosis, whichever occurred later, and ended at the first date of the EAM under study, death, emigration, 70 years of age, and 31 December 2016. Incidence rates (IRs) and incidence rate ratios were calculated for each EAM, and stratified by sex and age. Results: Incidence rate ratios for incident AU, IBD and psoriasis were significantly increased in AS (20.2, 6.2, 2.5), uSpA (13.6, 5.7, 3.8) and PsA (2.5, 2.3, n.a) vs controls. Men with AS and uSpA had significantly higher IRs per 1000 person-years at risk for incident AU than women with AS (IR 15.8 vs 11.2) and uSpA (IR 10.1 vs 6.0), whereas no such sex difference was demonstrated in PsA or for the other EAMs. Conclusions: AU, followed by IBD and psoriasis, is the EAM most strongly associated with AS and uSpA. Among the SpA subtypes, AS and uSpA display a largely similar pattern of EAMs, whereas PsA has a considerably weaker association with AU and IBD.
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| 9. |
- Bengtsson, Karin, 1980, et al.
(författare)
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Occurrence and relative risks for non-vertebral fractures in patients with ankylosing spondylitis compared with the general population: a register-based study from Sweden
- 2023
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Ingår i: Rmd Open. - : BMJ. - 2056-5933. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo estimate the incidence of non-vertebral fractures in ankylosing spondylitis (AS) compared with the general population.MethodsNationwide register-based cohort study including patients with AS (n=11 611, 65% men, mean age 48 years), and matched general population controls (n=58 050). Five prespecified fracture outcomes: (1) non-vertebral; (2) fracture of the proximal humerus, distal forearm or hip; (3) proximal humerus; (4) distal forearm and (5) hip) were identified through register linkages with follow-up 2007-2016. We used Poisson regression to calculate incidence rates (IRs), number of fractures per 1000 person-years at risk and IR ratios (IRRs), overall and by sex and age. IRRs were adjusted for history of any prior fracture.ResultsIRs (men/women) for non-vertebral fracture in AS were 11.9 (95% CI 11.0 to 12.9)/14.5 (95% CI 13.1 to 16.1) and in controls 10.0 (95% CI 9.7 to 10.4)/11.8 (95% CI 11.1 to 12.4), IRR (men/women) 1.2 (95% CI 1.1 to 1.3)/1.2 (95% CI 1.1 to 1.4). IRs (men/women) for fractures of the humerus, forearm or hip in AS were 4.0 (95% CI 3.5 to 4.6)/6.3 (95% CI 5.4 to 7.3) and in controls 2.7 (95% CI 2.5 to 2.9)/5.5 (95% CI 5.1 to 6.0), IRR (men/women) 1.5 (95% CI 1.3 to 1.7)/1.1 (95% CI 0.9 to 1.3). IRRs were statistically significantly elevated in men with AS versus controls for forearm fracture (1.4 (95% CI 1.1 to 1.7)) and hip fracture (1.8 (95% CI 1.4 to 2.3)), whereas not in women with AS where the IRRs were 1.1 (95% CI 0.9 to 1.4) and 1.0 (95% CI 0.6 to 1.4). For humerus fracture, IRRs were 1.4 (95% CI 0.99 to 1.9) in men with AS versus controls and 1.1 (95% CI 0.8 to 1.6) in women.ConclusionsBoth men and women with AS have a slightly higher risk of non-vertebral fractures than the general population. A statistically significantly higher risk of fractures of the proximal humerus, distal forearm or hip was found in men with AS in comparison to general population, where the relative risk was especially pronounced for hip fracture.
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| 10. |
- Flowers, Sarah A., et al.
(författare)
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Decrease of core 2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking
- 2020
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 295:47, s. 16023-16036
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Tidskriftsartikel (refereegranskat)abstract
- The synovial fluid glycoprotein lubricin (also known as proteoglycan 4) is a mucin-type O-linked glycosylated biological lubricant implicated to be involved in osteoarthritis (OA) development. Lubricin's ability to reduce friction is related to its glycosylation consisting of sialylated and unsialylated Tn-antigens and core 1 and core 2 structures. The glycans on lubricin have also been suggested to be involved in crosslinking and stabilization of the lubricating superficial layer of cartilage by mediating interaction between lubricin and galectin-3. However, with the spectrum of glycans being found on lubricin, the glycan candidates involved in this interaction were unknown. Here, we confirm that the core 2 O-linked glycans mediate this lubricin-galectin-3 interaction, shown by surface plasmon resonance data indicating that recombinant lubricin (rhPRG4) devoid of core 2 structures did not bind to recombinant galectin-3. Conversely, transfection of Chinese hamster ovary cells with the core 2 GlcNAc transferase acting on a mucin-type O-glycoprotein displayed increased galectin-3 binding. Both the level of galectin-3 and the galectin-3 interactions with synovial lubricin were found to be decreased in late-stage OA patients, coinciding with an increase in unsialylated core 1 O-glycans (T-antigens) and Tn-antigens. These data suggest a defect in crosslinking of surface-active molecules in OA and provide novel insights into OA molecular pathology.
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