| 1. |
- Andersson Sjöland, Annika, et al.
(author)
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Versican in inflammation and tissue remodelling: the impact on lung disorders.
- 2015
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In: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 25:3, s. 243-251
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Research review (peer-reviewed)abstract
- Versican is a proteoglycan that has many different roles in tissue homeostasis and inflammation. The biochemical structure is comprised of four different types of the core protein with attached glycosaminoglycans that can be sulphated to various extents and has the capacity to regulate differentiation of different cell types, migration, cell adhesion, proliferation, tissue stabilization and inflammation. Versican's regulatory properties are of importance during both homeostasis and changes that lead to disease progression. The glycosaminoglycans that are attached to the core protein are of the chondroitin sulfate/dermatan sulfate type and are known to be important in inflammation through interactions with cytokines and growth factors. For a more complex understanding of versican it is of importance to study the tissue niche, where the wound healing process in both healthy and diseased conditions take place. In previous studies our group has identified changes in the amount of the multifaceted versican in chronic lung disorders such as asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans syndrome, which could be a result of pathologic, transforming growth factor β driven, on-going remodelling processes. Reversely, the context of versican in its niche is of great importance since versican has been reported to have a beneficial role in other contexts e.g. emphysema. Here we explore the vast mechanisms of versican in healthy lung and in lung disorders.
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| 2. |
- Cagnotto, Giovanni, et al.
(author)
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Male Sex Predicts a Favorable Outcome in Early ACPA-Negative Rheumatoid Arthritis: Data From an Observational Study
- 2022
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In: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 49:9, s. 990-997
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The aim of the present study was to investigate whether the relationship between sex and clinical outcomes in early rheumatoid arthritis (RA) varies by autoantibody status. METHODS: Two inception cohorts of consecutive patients with early RA (ie, symptom duration ≤ 12 months) in the southern region of Sweden were investigated. Patients were stratified by anticitrullinated peptide antibody (ACPA) status. The primary outcome was remission (Disease Activity Score in 28 joints [DAS28] < 2.6) at 12 months. Secondary outcomes were remission at 6 months and European Alliance of Associations for Rheumatology good response at 6 and 12 months compared to baseline. In logistic regression models, which were adjusted for age, DAS28 values, and Health Assessment Questionnaire values at baseline, the relationship between sex and clinical outcomes, stratified by ACPA status, was investigated. RESULTS: In total, 426 patients with early RA were included: 160 patients were ACPA negative and 266 patients were ACPA positive. At 12 months, 27.1% (38/140) of females and 24.1% (13/54) of males with ACPA-positive RA achieved DAS28 remission. In ACPA-negative RA, 16.0% (13/81) of females and 48.6% (18/37) of males achieved DAS28 remission at 12 months. Males had higher odds of reaching remission at 12 months in the ACPA-negative patient group (pooled adjusted odds ratio [OR] 4.79, 95% CI 1.97-11.6), but not in the ACPA-positive group (pooled adjusted OR 1.06, 95% CI 0.49-2.30). CONCLUSION: Male sex was associated with better clinical outcomes in ACPA-negative early RA, but not in ACPA-positive early RA. The poor outcomes in females with early seronegative RA suggest that this represents a difficult-to-treat patient group. Copyright © 2022 by the Journal of Rheumatology.
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| 3. |
- Eberhard, Anna, et al.
(author)
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Radiographic damage in early rheumatoid arthritis is associated with increased disability but not with pain-a 5-year follow-up study
- 2023
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In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 25:1
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Journal article (peer-reviewed)abstract
- ObjectivesTo evaluate how radiographic damage, overall and measured as joint space narrowing score (JSNS) and erosion score (ES), as well as other clinical and laboratory measures, relate to disability and pain in early rheumatoid arthritis (RA).MethodsAn inception cohort of 233 patients with early RA, recruited in 1995-2005, was followed for 5 years. Disability was assessed with the Health Assessment Questionnaire (HAQ), and pain with a visual analogue scale (VAS; 0-100 mm). Radiographs of hands and feet were evaluated using the Sharp-van der Heijde score (SHS), including JSNS and ES. The relation for radiographic scores and other clinical parameters with pain and HAQ were evaluated cross-sectionally by multivariate linear regression analysis and over time using generalized estimating equations.ResultsES was significantly associated with HAQ cross-sectionally at inclusion, after 2 and after 5 years, and over time. Associations for HAQ with SHS and JSNS were weaker and less consistent compared with those for ES. There was no association between radiographic scores and pain at any visit. Both HAQ and pain were associated with parameters of disease activity. The strongest cross-sectional associations were found for the number of tender joints (adjusted p<0.001 at all visits).ConclusionJoint damage was associated with disability already in early RA. Erosions of hands and feet appear to have a greater influence on disability compared with joint space narrowing early in the disease. Pain was associated with other factors than joint destruction in early RA, in particular joint tenderness-suggesting an impact of pain sensitization.
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| 4. |
- Högelin, Emil Rydell, et al.
(author)
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Reliability and Validity of an Ultrasound-Based Protocol for Measurement of Quadriceps Muscle Thickness in Children
- 2022
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In: Frontiers in physiology. - : Frontiers Media SA. - 1664-042X. ; 13, s. 830216-
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Journal article (peer-reviewed)abstract
- Introduction and aims: Accurate determination of skeletal muscle size is of great importance in multiple settings including resistance exercise, aging, disease, and disuse. Ultrasound (US) measurement of muscle thickness (MT) is a method of relatively high availability and low cost. The present study aims to evaluate a multisite ultrasonographic protocol for measurement of MT with respect to reproducibility and correlation to gold-standard measurements of muscle volume (MV) with magnetic resonance imaging (MRI) in children.Material and methods: 15 children completed the study (11 ± 1 year, 41 ± 8 kg, 137 ± 35 cm). Following 20 min supine rest, two investigators performed US MT measurements of all four heads of the m. quadriceps femoris, at pre-determined sites. Subsequently, MRI scanning was performed and MV was estimated by manual contouring of individual muscle heads.Results: Ultrasound measurement of MT had an intra-rater reliability of ICC = 0.985–0.998 (CI 95% = 0.972–0.998) and inter-rater reliability of ICC = 0.868–0.964 (CI 95% = 0.637–0.983). The US examinations took less than 15 min, per investigator. Muscle thickness of all individual quadriceps muscles correlated significantly with their corresponding MV as measured by MRI (overall r = 0.789, p < 0.001).Conclusion: The results of this study indicate that US measurement of MT using a multisite protocol is a competitive alternative to MRI scanning, especially with respect to availability and time consumption. Therefore, US MT could allow for wider clinical and scientific implementation.
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| 5. |
- Lindegren, Camilla, et al.
(author)
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Intake of Dairy Products as a Risk Factor for Rheumatoid Arthritis; A Nested Case-Control Study
- 2022
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In: Arthritis & Rheumatology. - 2326-5205. ; 74:Suppl. 9
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Conference paper (other academic/artistic)abstract
- Background/Purpose: There has been increasing interest in diet as a factor that may contribute to the development of rheumatoid arthritis (RA). There is limited and somewhat contradictory information on the impact of dairy products in this context. The purpose of this study was to investigate the relation between intake of various dairy products and the risk of RA in a nested case-control study.Methods: Participants in a population-based survey conducted in 1991-1996 who were subsequently diagnosed with RA (from inclusion until December 2016) were identified through register linkage and validated in a structured review of case records. Four controls for each validated case, matched for sex, year of birth, and year of inclusion, were selected from the study cohort. The controls were alive and free of RA when the index person was diagnosed with RA. At inclusion in the survey, diet was assessed using a modified diet history method, consisting of a seven-day food record, a food questionnaire, and a structured interview. Reported intakes of dairy products were divided into groups based on quartiles, with the lowest quartile set as the reference in all analyses. Based on conditional logistical regression, including adjustments for total energy intake and for potential confounders that have been associated with diet and RA (i.e. current smoking, physical activity and alcohol intake), odds ratios (ORs) for RA were estimated, with 95% confidence intervals (CI). Potential misreporters of total energy intake were excluded. Assessed types of dairy products included regular (non-fermented) milk, fermented milk, cream, cheese, and butter.Results: There were 305 incident cases of RA (76 % females, 67 % anti-citrullinated protein antibody and/or rheumatoid factor positive, mean age 68.9 years at onset and mean duration of 12 years from screening to RA diagnosis). The group with highest intake of regular milk ( >398 g/day) had a significantly increased risk of RA (multi-adjusted OR 1.86; 95% CI 1.08-3.22). High intake of cheese with >11% fat ( >56 g/day) was inversely associated with risk of RA (adjusted OR 0.53; 95% CI 0.31-0.92) and a trend of lower risk across quartiles of cheese intake was observed. Intake of cream, fermented milk or butter did not have a significant impact on the risk of developing RA. Associations for intakes of cheese and regular milk with the risk of RA remained significant in multivariable analysis, including both exposures (Table 1).Conclusion: High intake of regular milk appears to increase the risk of RA, whereas high intake of cheese may reduce the risk. Potential explanations for these patterns include differential effects of dairy product depending on the extent of processing and fermentation, that may affect the gut microbiota and modulate the risk of developing RA.
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| 6. |
- Rydell, Emil, et al.
(author)
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Cardiovascular disease risk in early rheumatoid arthritis: the impact of cartilage oligomeric matrix protein (COMP) and disease activity
- 2023
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In: BMC Rheumatology. - 2520-1026. ; 7:1
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Journal article (peer-reviewed)abstract
- Background: To investigate whether baseline serum cartilage oligomeric matrix protein (COMP), patient characteristics, traditional cardiovascular disease (CVD) risk factors and disease activity over time predict CVD, in early rheumatoid arthritis (RA). Methods: This study included patients with early RA (< 12 months disease duration) (n = 233) recruited 1995–2005. Potential predictors of CVD and coronary artery disease (CAD) were assessed using Cox regression. Results: A first ever diagnosis of CVD occurred in 70 patients, and CAD in 52. Age, sex, hypertension and diabetes predicted CVD and CAD. COMP was associated with increased risk of CVD and CAD [crude hazard ratios (HRs) per SD 1.45; 95% CI 1.17–1.80 and 1.51; 95% CI 1.18–1.92, respectively]. When adjusted for age, sex, hypertension, diabetes and ESR, results where similar but did not reach significance [HRs 1.32, 95% CI 0.99–1.74 and 1.35, 95% CI 0.99–1.86]. Baseline disease activity did not independently predict CVD. High DAS28 (> 5.1) at two years was associated with increased risk of subsequent CVD [adjusted HR 2.58; 95% CI 1.10–6.04] and CAD. ESR and CRP at two years as well as cumulative disease activity over 2 years independently predicted CVD and CAD. Conclusion: COMP may be a novel predictor of CVD and CAD in RA. Active disease two years after RA diagnosis, as well as cumulative disease activity, was associated with increased risk of CVD and CAD, independent of traditional CVD risk factors. Awareness of the particularly increased CVD risk among difficult to treat patients is important in order to further reduce CVD in RA.
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| 7. |
- Rydell, Emil, et al.
(author)
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High Disease Activity over Time and Persistent Inflammation Are Associated with Increased Risk of Cardiovascular Disease in Patients with Early Rheumatoid Arthritis
- 2015
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In: Arthritis & Rheumatology. - 2326-5205. ; 67:Suppl. 10
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Conference paper (other academic/artistic)abstract
- Background/Purpose:Rheumatoid arthritis (RA) is associated with an increased rate of cardiovascular (CV) disease. Systemic inflammation has been implicated as a key factor behind CV comorbidity in RA. The objective of this study was to investigate the impact of disease activity and inflammation over the first two years on the risk of subsequent CV events in patients with early RA.Methods:An inception cohort of patients with early RA (symptom duration Results:A total of 207 patients with early RA (70 % women, mean age 62 years) were followed from the 24-month visit to the first CV event, migration from the region, death or Dec 31, 2011. CV events occurred in 54 patients during the follow-up. A high disease activity over the first two years (defined as AUC for DAS28 above the median) was associated with a significantly increased risk of CV events (age-sex adjusted hazard ratio (HR) 2.03; 95 % confidence interval (CI) 1.15-3.60). In separate analyses, it was demonstrated that patients with CRP at two years within the highest quartile (>11 mg/l) had a significantly higher risk of CV events compared to those with lower CRP values (age-sex adjusted HR 1.82; 95 % CI 1.04-3.17). Results were similar in models adjusted for smoking, hypertension and diabetes in addition to age and sex (multivariate adjusted HRs for DAS28-AUC above the median: 2.05 (95% CI 1.13-3.73); for CRP>11 mg/l: 1.90 (95% CI 1.06-3.42)).Conclusion:A high disease activity during the first two years after RA diagnosis and a high CRP at the two-year follow-up were both associated with a doubled risk of CV events. These findings suggest that patients with persistently active RA are at particularly increased risk, and highlight the importance of disease control for CV prevention in patients with early RA.
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| 8. |
- Rydell, Emil, et al.
(author)
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LEVELS OF IL-6 AND OTHER INFLAMMATORY PROTEINS IN EARLY RA PREDICT JOINT DAMAGE PROGRESSION OVER 5 YEARS
- 2022
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 81:Suppl. 1, s. 504-505
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Conference paper (other academic/artistic)abstract
- Background Joint damage in rheumatoid arthritis (RA) remains a significant problem. Identification of biomarkers associated with joint destruction can improve our understanding of underlying disease processes and future management.Objectives To evaluate inflammatory proteins as potential predictors of radiographic progression of joint damage.Methods Consecutive early RA patients (symptom duration 0.50 were investigated as potential predictors of radiographic progression. Logistic and linear regression models were used to assess associations with rapid radiographic progression (RRP; ≥5 SHS/year) and progression of SHS over 5 years.Results Data on baseline levels of proteins, and radiographs at baseline and 5 years were available for 114 patients. The median progression of SHS was 11 (interquartile 2-19). For potential biomarkers with an a priori hypothesis, IL-6 significantly predicted both RRP and progression of SHS over 5 years analyzed as a continuous variable [adjusted ß = 0.09 per SD, p=0.032, adjusted for rheumatoid factor (RF) and baseline SHS]. A significant positive association for matrix metalloproteinase 1 (MMP-1) was observed in the unadjusted analysis for SHS progression, but not for RRP (Table 1). In the exploratory analyses, S100 calcium-binding protein A12 (EN-RAGE) was positively, and TNF-related apoptosis-inducing ligand (TRAIL) negatively associated with both outcomes.Conclusion Plasma levels of IL-6 at RA diagnosis predict degree of future joint damage. EN-RAGE and TRAIL, both modulators of NF-κB which is known to regulate immune response, are potential biomarkers that need further investigation.
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| 9. |
- Rydell, Emil, et al.
(author)
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Plasma Inflammatory Protein Biomarkers May Predict Cardiovascular Events in Early Rheumatoid Arthritis
- 2022
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Conference paper (other academic/artistic)abstract
- Background/Purpose: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD). Systemic inflammation, driven by cytokines such as TNF, IL-6 and IL-17A, has been implicated as a contributing factor to CVD development in RA. The objective of this study was to investigate the impact of 92 inflammatory proteins on the risk of CVD events in patients with early RA.Methods: Consecutive patients with early RA patients (symptom duration < 12 months), recruited 1995-2005 from a defined area, were followed in an observational study. Stored plasma samples from the baseline visit were analyzed for levels of 92 inflammatory proteins (Inflammation panel by O-link). Data on CVD events (coronary-, cerebrovascular- and peripheral artery disease) were retrieved from the Swedish national inpatient- and cause of death registries from 1969-2019. Statistical analyses were pre-designated as hypothesis-driven (Table 1) or exploratory. For the latter, principal component analysis was used to identify groups of proteins that explain the variance in the proteome. Within components selected based on Eigenvalues, proteins with a factor loading of >0.50 were investigated as potential predictors of CVD events. Protein levels were standardized to facilitate comparison. Patients with CVD events before RA diagnosis were excluded from the analyses. Primary outcome was the first CVD event, and secondary outcome was the first coronary artery disease (CAD) event during follow-up. Cox regression models (crude and age-sex adjusted) were used to assess the relationship between baseline biomarkers and outcomes. Models with significant predictors were further adjusted for ESR, to assess independent inflammatory pathways. For a priori hypothesis-based analyses, multiple testing was taken into account using Holm’s correction.Results: Baseline levels of proteins were available for 163 patients. A first ever CVD event occurred in 47 patients during follow-up, and a first ever CAD event in 37 patients. Among potential biomarkers with an a priori hypothesis, levels of IL-17A were significantly associated with overall CVD events in the crude and age-sex adjusted models (Table 1), and when additionally adjusted for baseline levels of ESR [adjusted hazard ratio 1.34; 95% confidence interval 1.03-1.76), while the associations did not reach significance for CAD events (Table 1). Osteoprotegerin (OPG) levels were significantly associated with both outcomes in crude, but not in adjusted models (Table 1). There were no such associations for IL-6, TNF, Monocyte Chemotactic Protein (MCP) 1 or IL-8 (Table 1). In the exploratory analyses, several proteins, in particular MCP-3, had significant associations with CVD and CAD events, but only in the unadjusted models (Table 2).Conclusion: Plasma levels of IL-17A at RA diagnosis predicted future CVD events, although we cannot exclude that this finding is due to multiple testing. The observed association was independent of levels of systemic inflammation, measured by ESR, suggesting a particular role for IL-17A in mechanisms leading to CVD. OPG and MCP-3 may also be predictive of CVD in patients with RA and should be further investigated.Supporting image 1Supporting image 2Disclosures: E. Rydell, None; L. Jacobsson, Novartis, Eli Lilly, Janssen; C. Turesson, AbbVie/Abbott, Nordic Drugs, Bristol-Myers Squibb(BMS).
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| 10. |
- Rydell, Emil, et al.
(author)
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PREDICTORS OF EROSION AND JOINT SPACE NARROWING PROGRESSION IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS
- 2019
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In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd and European League Against Rheumatism. - 1468-2060. ; 78:Suppl. 2, s. 1043-1043
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Conference paper (other academic/artistic)abstract
- Background: Joint damage in rheumatoid arthritis (RA) includes erosions and joint space narrowing (JSN). Predictors of these processes, and the underlying mechanisms, require further study1.Objectives: To investigate the relation between patient characteristics at RA diagnosis and progression of erosions and JSN, over 5 years. Methods: Consecutive early RA patients (symptom duration Results: 233 early RA patients where included. Radiographs at baseline and 5 years were available for 162 patients. Results on predictors of rapid radiographic progression of the total SHS have been reported previ- ously2. The median (interquartile) progression of erosion and JSN scores were 4 (0-8) and 8 (1-16), respectively. RF and anti-CPP predicted pro- gression of erosions and JSN over 5 years, with stronger associations for erosions (Table 1). Baseline erosion- and JSN scores each predicted progression of JSN, while baseline JSN did not predict progression of erosions. In crude analyses, higher disease activity, CRP and ESR were associated with progression of both erosions and JSN, while statistically more robust for the former. Smoking and high levels of Cartilage Oligo- meric Matrix Protein (COMP) (>12 U/L) were both associated with pro- gression of erosions ((B= 0.12, p= 0.016) and (B= 0.12, p= 0.02) respectively) but not JSN, in adjusted analyses (Table 1). Overweight or obesity (BMI >25kg/m2) was associated with less progression of JSN (B= -0.14, p= 0.018, adjusted for RF, age and baseline JSN score).Conclusion: RF, anti-CCP and markers of inflammation and disease activity predicted progression of erosions and JSN, in particular erosions. Development of erosions may predate cartilage damage leading to JSN. Smoking and high baseline levels of COMP predicted progression of ero- sions, but not JSN. Overweight and obesity may be associated with mechanisms that protect from JSN.
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