| 1. |
- Do, Lan, et al.
(author)
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Anti-CD74 IgA autoantibodies in radiographic axial spondyloarthritis : a longitudinal Swedish study
- 2021
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In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332 .- 1310-0505. ; 60:9, s. 4085-4093
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Antibodies against anti-CD74 are related to axial spondyloarthritis (axSpA). The objectives were (i) to study IgA anti-CD74 in radiographic (r)-axSpA patients in the Backbone cohort and to calculate the sensitivity and specificity of anti-CD74, (ii) to study the fluctuation of IgA anti-CD74 levels in prospectively collected samples, and (iii) to explore the relation between IgA anti-CD74 and radiographic spinal changes.METHODS: IgA anti-CD74 was analysed by ELISA in 155 patients with r-axSpA and age- and sex-matched controls. BASDAI, ASDAS, BASFI and BASMI were assessed and spinal radiographs were scored for r-axSpA-related changes with mSASSS. Previously donated samples, before inclusion in the Backbone study, were identified in the Medical Biobank of Northern Sweden.RESULTS: A total of 155 patients comprising 69% men and 31% women, age [mean (s.d.)] 55.5 (11.4) years and 152 (98.1%) HLA-B27 positive, were included. The plasma level of IgA anti-CD74 was significantly higher in the patients [median (interquartile range), 12.9 (7.9-17.9) U/ml] compared with controls [10.9 (7.2-14.6) U/ml, P = 0.003]. IgA anti-CD74 was above the cut-off level of 20 U/ml in 36/155 (23.2%) patients and in 15/151 (9.9%) controls (P = 0.002). Multivariable logistic regression analyses revealed ≥1 syndesmophyte associated with IgA anti-CD74 (odds ratio 5.64; 95% CI: 1.02, 35.58; P = 0.048) adjusted for hsCRP, smoking, BMI, sex and age. No distinct pattern of IgA anti-CD74 over time was revealed.CONCLUSION: Plasma levels of IgA anti-CD74 were increased in r-axSpA and independently associated with radiographic spinal changes, which suggests that IgA anti-CD74 could play a role in the pathogenies of r-axSpA.
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| 2. |
- Forsblad-D'elia, H., et al.
(author)
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DECREASED LEVELS OF T FOLLICULAR HELPER (CD4+CXCR5+) CELLS AND CD27+CD38+ AND CD27+CD38- B CELLS IN ANKYLOSING SPONDYLITIS PATIENTS CORRELATE WITH MARKER OF INFLAMMATION
- 2021
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In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80:Suppl 1, s. 13-14
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Journal article (other academic/artistic)abstract
- The role of different lymphocyte subsets in ankylosing spondylitis (AS) is still to be elucidated. It has previously been reported contradictory data concerning the levels of T Follicular Helper (TFH) cells and differentiated B cells in peripheral blood of AS patients. In addition, the connection to disease related parameters is still to be fully revealed.Objectives:The purpose of this study was to investigate the level of CD4+TFH cells and CD27+CD38+/CD38- B cells in patients with AS from northern Sweden and to compare the levels with age and sex-matched controls. We also studied associations between these cell subsets and disease related factors.Methods:Peripheral blood mononuclear cells (PBMSc) from a cohort of 50 patients with AS from Region Västerbotten (mean age 52±9.1 years, 33 (66 %) men, 50 (100 %) HLAB27 positive) and 50 pair wise matched blood donor controls (mean age 54±8.8 years, 33 (66 %) men) were stained with a combination of antibodies allowing for the detection of CD27, CD38, CD19, CD3, CD4 and CXCR5 markers and analyzed by flow cytometry. In addition, the patient with AS were examined with spinal x-ray for radiographic alterations assessed with mSASSS. CRP and ESR were measured and physical function and disease activity were registered with BASMI and BASFI respectively ASDAS-CRP and BASDAI.Results:When comparing AS patients and controls pair wise, we observed on average a 50% reduction of TFH (CD3+CD4+CXCR5+) cells among CD45+ lymphocytes in PBMCs from patients (p=0,000008). Furthermore, a 20-30% reduction among memory/plasma cells (CD19+CD27+CD38+ and CD19+CD27+CD38-) among CD45+ lymphocytes in PBMCs from patients (p=0,002 and p=0,007 respectively). For female patients a correlation between TFH and ESR (Rs=-0,551 p=0,022) was observed. Moreover, negative correlations between the two B cell subsets (CD19+CD27+CD38+ and CD19+CD27+CD38-) and ESR were observed for female patients (Rs =–0,476 p=0,053 and Rs =–0,522 p=0,032 respectively).Conclusion:TFH cells was reduced in AS patients and this reduction correlated with a reduction in differentiated (CD27+CD38+ and CD27+CD38-) B cells. In addition, the inflammation marker ESR was negatively correlated with TFH as well as with the differentiated B cell subsets in female patients. Our observations indicates a role of the humoral immune response in AS.Disclosure of Interests:None declared
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| 3. |
- Hellman, Urban, 1966-, et al.
(author)
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Presence of hyaluronan in lung alveoli in severe Covid-19 : an opening for new treatment options?
- 2020
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In: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 295:45, s. 15418-15422
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Journal article (peer-reviewed)abstract
- Severe corona virus disease 2019 (Covid-19) is characterized by inflammation of the lungs with increasing respiratory impairment. In fatal Covid-19, lungs at autopsy have been filled with a clear liquid jelly. However, the nature of this finding has not yet been determined.The aim of the study was to demonstrate if the lungs of fatal Covid-19 contain hyaluronan as it is associated with inflammation and acute respiratory distress syndrome (ARDS) and may have the appearance of liquid jelly.Lung tissue obtained at autopsy from three deceased Covid-19 patients was processed for hyaluronan histochemistry using a direct staining method and compared with staining in normal lung tissue.Stainings confirmed that hyaluronan is obstructing alveoli with presence in exudate and plugs, as well as in thickened perialveolar interstitium. In contrast, normal lungs only showed hyaluronan in intact alveolar walls and perivascular tissue. This is the first study to confirm prominent hyaluronan exudates in the alveolar spaces of Covid-19 lungs, supporting the notion that the macromolecule is involved in ARDS caused by SARS-CoV-2. The present finding may open up for new treatment options in severe Covid-19, aiming at reducing the presence and production of hyaluronan in the lungs.
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| 4. |
- Law, Lucy, et al.
(author)
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Increased carotid intima-media thickness in patients with radiographic axial spondyloarthritis compared to controls and associations with markers of inflammation
- 2024
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In: CLINICAL RHEUMATOLOGY. - : Springer Nature. - 0770-3198 .- 1434-9949.
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Journal article (peer-reviewed)abstract
- Objective There is an increased risk for cardiovascular disease (CVD) in patients with radiographic axial spondyloarthritis (r-axSpA). In this cross-sectional study, we aimed to, overall and stratified by sex, (i) compare ultrasound derived carotid intima media thickness (cIMT), between patients and controls, and (ii) investigate associations between cIMT, clinical disease activity and inflammation-related laboratory markers in patients with r-axSpA. Method In total, 155 patients diagnosed with r-axSpA using the modified New York criteria and 400 controls were included. Bilateral carotid ultrasound, laboratory testing, and questionaries were acquired. Disease-specific assessments were carried out for patients. Linear regression analysis was used to assess associations. Results Linear regression analyses showed that patients with r-axSpA had increased mean cIMT compared to controls (mean +/- SD, 0.8 +/- 0.1 mm vs 0.7 +/- 0.1 mm, respectively, unstandardized beta (95% CI) -0.076 (-0.10, -0.052), P < 0.001) adjusted for smoking status and age. Linear regression analyses for patients with r-axSpA showed that only males presented significant associations between cIMT and inflammation-related laboratory markers, white blood cell (WBC) count (mean +/- SD, 6.8 +/- 1.6 10(9)/L) and monocytes (0.6 +/- 0.2 10(9)/L); WBC count (unstandardized beta (95% CI) 0.019 (0.0065, 0.031), P = 0.003, R-2 = 0.57) and monocytes (0.13 (0.0047, 0.26), P = 0.041, R-2 = 0.55), adjusted for age, smoking status, body mass index, hypertension, dyslipidemia, diabetes mellitus, ASDAS-CRP, and treatment with DMARDs and glucocorticoids. No significant association was found between cIMT and clinical disease activity assessed by ASDAS-CRP. Conclusion Patients with r-axSpA had significantly increased cIMT compared to controls. In male patients, higher WBC and monocyte count were associated with an increase in cIMT suggesting the role of inflammation in the development of atherosclerosis.
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| 5. |
- Lejon, Kristina, 1967-, et al.
(author)
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Decreased levels of T follicular helper (CD4+CXCR5+) cells and CD27+CD38+and CD27+CD38-B cells in ankylosing spondylitis patients correlate with markers of inflammation
- 2023
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In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 97:1
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Journal article (peer-reviewed)abstract
- The purpose of this study was to study CD4+CXCR5+ T follicular helper (TFH) cells, CD27+CD38+ plasmablasts and CD27+CD38- memory B cells, as well as disease-related factors in patients with ankylosing spondylitis (AS) from northern Sweden. Peripheral blood mononuclear cells (PBMC) from 50 patients with AS (mean age 52 +/- 9 years, 66% men, 100% HLA-B27 positive) and 50 pairwise matched blood donor controls (mean age 54 +/- 9 years, 66% men) were stained with antibodies for CD27, CD38, CD19, CD3, CD4 and CXCR5 markers and analysed by flow cytometry. Patients with AS were examined with spinal x-ray for radiographic alterations (mSASSS), and plasma levels of C-reactive protein, erythrocyte sedimentation rate, as well as selected proinflammatory and regulatory cytokines were determined. Physical mobility, function and disease activity were registered by BASMI, BASFI and ASDAS-CRP, BASDAI, respectively. Comparing AS patients and controls pairwise, we observed a 56% reduction of TFH cells in PBMCs from AS patients (P = .000008). Furthermore, a 20%-30% reduction in plasmablasts and B memory cells (P <= .002 and P <= .007, respectively) was observed. In female patients, negative correlations between ESR and TFH, plasmablasts and B memory cells were observed; Rs = -0.551, P <= .02; Rs = -0.476, P <= .05 and Rs = -0.522, P <= .03, respectively. In addition, positive correlations between the regulatory cytokine IL-10 and the proportion of B cells, IL-22, and the proportion of plasmablasts as well as a negative correlation between levels of the proinflammatory cytokine IL-6 and TFH were detected. Our observations indicate a role of an aberrant humoral immune response related to inflammation in AS.
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| 6. |
- Lejon, Kristina, 1967-, et al.
(author)
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Increased Proportion of TH17, TH22 and TC17 Cells and the Correlation to IL-22 and Clinical Parameters in Patients with Ankylosing Spondylitis from Northern Sweden
- 2020
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In: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 72
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Journal article (other academic/artistic)abstract
- Background/Purpose: Increased levels of TH17 and TH22 as well as TC17 and TC22 cells have previously been associated with ankylosing spondylitis (AS). The correlation between these inflammatory T cell subsets and clinically relevant parameters as well as cytokines has also been reported. However, the status of these inflammatory cells in a well characterized AS cohort from northern Sweden has not been studied. The purpose of this study was to confirm the increased presence of inflammatory T cell subsets in peripheral blood of patients with AS from northern Sweden in relation to age and sex-matched controls. In addition, associations of clinically relevant parameters with the level of the inflammatory T cell subset(s) and cytokines of interest were performed.Methods: Peripheral blood mononuclear cells (PBMCs) from a cohort of 50 patients with AS from Region Västerbotten (Modif NY, mean age 52±9.1 years, 33 (66 %) men, 50 (100 %) HLAB27) and 50 pair wise matched blood donor controls (mean age 54±8.8 years, 33 (66 %) men) were stained with a combination of antibodies allowing for the detection of surface expressed CD45, CD3, CD4, CD8, intracellular IL-17 and IL-22 and analyzed by flow cytometry. In addition, levels of IL-17 and IL-22 in plasma were determined by the Meso Scale Discovery platform. The patient with AS were examined with spinal x-ray for radiographic alterations assessed with mSASSS. CRP and ESR were measured and physical function and disease activity were registered with BASMI and BASFI respectively ASDAS-CRP and BASDAI.Results: Pair wise comparison of AS patients and controls showed a 1,5 to 2-fold increase of TH17, TH22 and TC22 cells among CD45+CD3+ lymphocytes in PBMCs of male patients (p=0,013, p=0,003 and p=0,024 respectively). Levels of IL-22 in plasma and proportion of TC17 correlated in male patients (Rs=0,499 p=0,003) and plasma levels of IL10 showed an inverse correlation in relation to TC17 in all patients (Rs=-0,276 p=0,05). In female AS patients there was a negative correlation between TC22 and CRP (Rs = -0,573, p=0,016). In addition, after splitting the group of female into pre- and postmenopausal correlation between TC17 and mSASSS (Rs = 0,845, p=0,034), TC22 and BASFI (Rs = 0,986, p=0,0003) (premenopausal) and TC22 and BASMI (Rs = 0,764, p=0,006) (postmenopausal) was observed.Conclusion: We confirm an increased proportion of TH17, TH22 and TC17 cells in blood in AS male patients from northern Sweden. In addition, positive correlation of the proinflammatory cytokine IL-22 and negative correlation of anti-inflammatory cytokine IL-10 in relation to TC17 corroborate the influence of these cells in the disease process. Interestingly, in female AS patients there was a correlation between clinical relevant parameters to particular inflammatory T cell subset dependent on the menopausal status, suggesting a role of female sex hormones in AS pathogenesis.
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| 7. |
- Lejon, Kristina, 1967-, et al.
(author)
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Increased proportions of inflammatory T cells and their correlations with cytokines and clinical parameters in patients with ankylosing spondylitis from northern Sweden
- 2022
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In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 96:3
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Journal article (peer-reviewed)abstract
- Ankylosing spondylitis (AS) is an autoimmune disease affecting parts of the skeletal structure in particular. Previously increased levels of the inflammatory cell types Th17, Th22, Tc17 and Tc22 cells have been shown to be associated with AS. Here, we analysed the levels of inflammatory T cell subsets, related cytokines and clinical characteristics of AS patients vs controls from northern Sweden. Peripheral blood mononuclear cells (PBMCs) obtained from 50 AS patients and 50 matched controls were short term stimulated with PMA/Ionomycin, stained and analysed by flow cytometry. Plasma levels of Interleukin (IL)-17, IL-22, IL-10 as well as clinically relevant markers were determined. Compared to male controls, male AS patients showed 1.5- to 2-fold increases of Th17 (P = .013), Th22 (P = .003) and Tc22 (P = .024) among CD45(+)CD3(+) lymphocytes. Plasma IL-22 levels correlated with the Tc17 proportion in male patients (R-s = 0.499, P = .003) and plasma IL-10 levels were inversely correlated with Tc17 among all patients (R-s = -0.276, P = .05). Male patients with syndesmophytes showed significantly higher Th17 proportions (P = .038). In female AS patients, Tc22 was negatively correlated with C-reactive protein (high sensitivity) (hsCRP) (R-s = -0.573, P = .016). We confirmed increased proportions of inflammatory T cells and correlations with relevant cytokines from male AS patients. The correlation between Th17 and syndesmophytes supports a role of Th17 in the pathogenic process.
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| 8. |
- MacLeod, Rebecca, et al.
(author)
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Selective isolation of hyaluronan by solid phase adsorption to silica
- 2022
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In: Analytical Biochemistry. - : Academic Press. - 0003-2697 .- 1096-0309. ; 652
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Journal article (peer-reviewed)abstract
- A solid phase adsorption method for selective isolation of hyaluronan (HA) from biological samples is presented. Following enzymatic degradation of protein, HA can be separated from sulfated glycosaminoglycans, other unsulfated glycosaminoglycans, nucleic acids, and proteolytic fragments by adsorption to amorphous silica at specific salt concentrations. The adsorbed HA can be released from silica using neutral and basic aqueous solutions. HA ranging in size from ∼9 kDa to MDa polymers has been purified by this method from human serum and conditioned medium of cultured cells.
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| 9. |
- Mörner, Stellan, et al.
(author)
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Ärftliga hjärt–kärlsjukdomar – ett multidisciplinärt arbetssätt krävs : [Experiences from a multidisciplinary cardiogenetic clinic]
- 2021
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In: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 118:40
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Journal article (peer-reviewed)abstract
- Comprehensive genetic and clinical care of families with monogenic cardiovascular diseases requires competences from different medical specialties. Genetic assessment, cascade screening, risk estimation, treatment and follow-up is difficult to cover. Fourteen years ago, a center for cardiovascular diseases was created in our hospital, to improve the care of families with monogenic cardiovascular diseases. At our center, clinical geneticists, cardiologists, angiologists, pediatric cardiologists and genetic counselors work together in a seamless organization, while still having different clinic affiliations. A key feature of this organization are the family outpatient clinics, where the proband and his/her relatives at genetic risk are invited to take part. When the family or relatives live in other parts of the country, they are invited to participate through video conference. In this paper we report our experiences and working routines from more than 300 families and 2000 individuals.
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| 10. |
- Olsson, Malin, et al.
(author)
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Metabolomics analysis for diagnosis and biomarker discovery of transthyretin amyloidosis
- 2021
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In: Amyloid. - : Taylor & Francis Group. - 1350-6129 .- 1744-2818. ; 28:4, s. 234-242
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Journal article (peer-reviewed)abstract
- Untargeted metabolomics is a well-established technique and a powerful tool to find potential plasma biomarkers for early diagnosing hereditary transthyretin amyloidosis. Hereditary transthyretin amyloidosis (ATTRv) is a disabling and fatal disease with different clinical features such as polyneuropathy, cardiomyopathy, different gastrointestinal symptoms and renal failure. Plasma specimens collected from 27 patients with ATTRv (ATTRV30M), 26 asymptomatic TTRV30M carriers and 26 control individuals were subjected to gas chromatography (GC)- and liquid chromatography (LC)-mass spectrometry (MS)-based metabolomics analysis. Partial least squares discriminant and univariate analysis was used to analyse the data. The models constructed by Partial least squares-discriminant analysis (PLS-DA) could clearly discriminate ATTRV30M patients from controls and asymptomatic TTRV30M carriers. In total, 24 plasma metabolites (VIP > 1.0 and p <.05) were significantly altered in ATTRV30M patient group (6 increased and 18 decreased). Eleven of these distinguished the ATTRV30M group from both controls and TTRV30M carriers. Plasma metabolomics analysis revealed marked changes in several pathways in patients with ATTRV30M amyloidosis. Statistical analysis identified a panel of biomarkers that could effectively separate controls/TTRV30M carriers from ATTRV30M patients. These biomarkers can potentially be used to diagnose patients at an early stage of the disease.
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