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- Hafstrom, I., et al.
(författare)
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A Swedish register-based, long-term inception cohort study of patients with rheumatoid arthritis - results of clinical relevance
- 2019
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Ingår i: Open Access Rheumatology-Research and Reviews. - 1179-156X. ; 11, s. 207-217
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: At the end of the twentieth century, the outcome of rheumatoid arthritis (RA) was shown to be unsatisfactory and new therapeutic strategies were introduced. This initiated a register-based long-term study of early RA, the Better Anti-Rheumatic PharmacOTherapy (BARFOT) study. The aims were to evaluate the disease course and to acquire knowledge for improved care. Patients and methods: BARFOT is a multicentre observational study of patients with early RA, consecutively included 1992-2006. The patients are followed in daily practice according to a structured protocol for 15 years and data recorded in a web-based register. Also, through linkage of the BARFOT register to national registers we have acquired information on comorbidity and mortality. Results: In all, 2857 patients have been included and over 80 scientific articles have been published. Phenotypic characteristics at disease onset, i.e. gender, smoking habits and autoantibody profiles have been addressed. The disease course over 15 years was described. Early predictors for persistent disease activity, impaired function, joint damage and comorbidities have been identified. Treatment strategies have been studied. A randomized sub-study gave strong support for the treatment of recent RA with low-dose prednisolone in combination with disease-modifying anti-rheumatic drug. Furthermore, the impact of lifestyle factors, such as smoking, alcohol consumption, body weight and physical activity has been addressed. Conclusion: A register-based study like BARFOT has provided a basis for optimal long-term management of patients with RA. In addition, the register has made it possible to perform a diversity of studies of RA addressing various issues of major relevance to the patients.
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- Sun, J., et al.
(författare)
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Effects of Atorvastatin on T-Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C-Reactive Protein and Interleukin 6
- 2021
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Ingår i: ACR Open Rheumatology. - : Wiley. - 2578-5745. ; 3:9, s. 642-653
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We study activation of T helper 17 (Th17) and regulatory T (Treg) cells and induction of apoptosis in cells from patients with systemic lupus erythematosus (SLE) compared with controls and effects of atorvastatin and its simulated interactions with other compounds. Methods: Mononuclear cells from 10 patients with SLE and 10 controls were cultured in conditions that induce Th17 and/or Treg cell polarization and/or apoptosis and were studied by FACScan. Gene expression was determined by quantitative real-time reverse transcription–polymerase chain reaction. Cytokines in plasma were determined by enzyme-linked immunosorbent assay. The Search Tool for Interactions of Chemicals (STITCH) was used to retrieve information regarding the binding properties of atorvastatin. Results: Among patients with SLE, the proportion of Th17 (CD4+IL17+) cells was higher compared with controls after activation, with Th17 or Treg polarizing cytokines, phorbol myristate acetate, and ionomycin. In contrast, Treg cells (CD4+CD25+CD127dim/−) frequencies were lower. CD95 stimulation induced relatively more apoptosis in Treg cells and less in Th17 cells, as compared with controls. Addition of atorvastatin normalized Th17/Treg cell balance and apoptosis induction. Accordingly, the ratio of RORC/FoxP3 decreased in patients with SLE. Interleukin 17 and interleukin 6 (IL-6) levels were increased in patients with SLE. Atorvastatin interacted strongly with C-reactive protein (CRP) and also significantly with IL-6. Conclusion: There is a higher proportion of Th17 cells and a lower proportion of Treg cells in patients with SLE after activation. Th17 cells were more resistant than Treg cells to CD95-induced apoptosis in SLE. Atorvastatin normalized these effects. Our findings reveal a novel mechanism behind the imbalance of Th17/Treg cells with implications for treatment in SLE. We determine for the first time simulated interaction between atorvastatin, CRP, and IL-6, implying a novel role of atorvastatin.
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- Ajeganova, S, et al.
(författare)
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Carotid atherosclerosis, disease measures, oxidized low-density lipoproteins, and atheroprotective natural antibodies for cardiovascular disease in early rheumatoid arthritis -- an inception cohort study
- 2012
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Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 39:6, s. 1146-1154
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Tidskriftsartikel (refereegranskat)abstract
- Although an enhanced risk of cardiovascular disease (CVD) in persons with rheumatoid arthritis (RA) is well established, the mechanisms behind it remain unclear. We studied whether carotid atherosclerosis, RA disease measures, or potential cardiovascular biomarkers influenced the incidence of CVD in an RA inception cohort.Methods.RA disease measures and CVD biomarkers were assessed at 0, 3, 12, 24, and 60 months after disease onset, and carotid ultrasonography after 5 years. The study outcome was incident CVD events — acute myocardial infarction, angina pectoris, congestive heart failure, or ischemic cerebrovascular event. Survival analysis and Cox and longitudinal regressions were used for statistical analyses.Results.A total of 105 patients, without CVD events prior to RA onset, experienced 17 CVD events, an incidence rate of 1.35 events per 100 person-years (95% CI 0.71–2.0). The rate of CVD events did not differ with regard to measures of carotid intima-media thickness, but it was higher for patients with bilateral carotid plaques than for those without (p = 0.012). Improvement in Disease Activity Score for 28 joints, visual analog scale for pain, and Stanford Health Assessment Questionnaire score over the first year, as well as usage of methotrexate (MTX), was associated, independent of age, with reduction of risk of CVD event [hazard ratios 0.68 (95% CI 0.5–0.97), 0.97 (95% CI 0.95–0.99), 0.35 (95% CI 0.15–0.82), and 0.34 (95% CI 0.12–0.91), respectively]. In longitudinal analyses, increasing oxidized low-density lipoprotein (oxLDL) and probability for low antiphosphorylcholine antibodies (anti-PC) were observed in those who experienced a subsequent CVD event.Conclusion.Bilateral carotid plaques were associated with poor CVD-free survival. Early reductions of inflammation, pain, and disability as well as MTX usage were associated with better CVD outcome. Elevated oxLDL and low IgM anti-PC levels may link chronic inflammation in RA to enhanced risk of CVD events.
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- Ajeganova, S, et al.
(författare)
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Dr. Ajeganova and Dr. Hafström reply
- 2013
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Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 40:3, s. 337-338
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Ajeganova, S, et al.
(författare)
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HIGHER LEVELS OF NATURAL ANTI-PHOSPHORYLCHOLINE ANTIBODIES ARE ASSOCIATED WITH LOWER RISK OF INCIDENT CARDIOVASCULAR EVENTS IN YOUNGER PATIENTS WITH RHEUMATOID ARTHRITIS
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 939-939
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The increased cardiovascular (CV) risk in rheumatoid arthritis (RA), especially in seropositive RA, is not fully explained by traditional risk factors. Immuno-inflammatory mechanisms and autoantibodies could be involved in the pathogenesis of atherosclerotic disease. Recent studies have suggested that anti-phosporylcholine antibodies (anti-PC) of IgM subclass counteract the generation of senescent and IL-17+ T-cells, have atheroprotective effects and may play a role in formation and stabilization of atherosclerotic plaque.Objectives:To investigate the association between IgM anti-PC antibodies with cardiovascular (CV) morbidity in patients with RA in age and sex groups and by serostatus.Methods:The study population was derived from the BARFOT early RA cohort, recruited in 1994-1999. The outcome was CV events i.e. AMI, angina pectoris, coronary intervention, ischemic stroke and TIA tracked through the Swedish Hospital Discharge and the National Cause of Death Registries. The RA-disease measures and traditional risk factors were assessed according to the protocol. Sera collected at inclusion and the 2-year visit were analyzed with ELISA to determine levels of anti-PC IgM (Athera CVDefine kit, Athera Biotechnologies AB). The Kaplan-Meier estimates and Cox proportional-hazards regression models were applied. Analysis were stratified by median level of IgM anti-PC and performed within strata of age, sex and RA-autoantibodies.Results:In all, 654 patients with early RA, 68% women, mean (SD) age 55(14.7) years, DAS28 5.2(1.3), 60% RF-positive and 60% ACPA-positive without prevalent CVD were included in this analysis. The level of IgM anti-PC at baseline was median (IQR) of 60.9(36.4-94.9) and at 2 years 56.0(32.3-84.2) U/ml. During follow-up of > 10 years, 141 incident CV events (21.6%) were registered. The levels of anti-PC both at inclusion and after 2 years of observation were lower in participants who experienced CV event than in those who did not, p=0.020 and p=0.012.The CV event-free survival differed between patients with levels of anti-PC above median compared with those with levels below, p=0.003 by log-rank test. The risk for incident CV event showed a 0.6-fold hazard (95% CI, 0.4-0.8) among patients with higher anti-PC levels as compared with those with lower levels, p=0.003. In the age groups, the risk for incident CV event was lower in patients aged <55 years at inclusion than in those who were older, hazard ratio (HR) 0.40 (0.17-0.94), p=0.036. This result persisted when adjusted for sex and all traditional risk factors, HR 0.36 (0.14-0.92), p=0.032. Also, the risk for incident CV events was lower in patients with higher anti-PC levels in females, HR 0.61 (0-39-0.45), and double RF- and ACPA- negative patients, 0.44 (0.21-0.90), in crude analyses.The favourable effect of anti-PC at baseline and the CV outcome was not observed in ages >55 years, males, ACPA+ and RF+ patients. There were no significant association between anti-PC level at 2 years and outcome.Conclusion:These results suggest that higher levels of IgM anti-PC are associated with a lower risk of incident CV events over 10 years in younger patients. The favourable atheroprotective effect of IgM anti-PC may be a part of explanation of lower risk of atherosclerotic disease in younger persons, females and in those with seronegative RA.Acknowledgments :6th Framework Program of the European Union (grant LSHM-CT-2006-037227 CVDIMMUNE)Disclosure of Interests:Sofia Ajeganova: None declared, Maria Andersson: None declared, Johan Frostegård Grant/research support from: Unconditional competitive grant from Amgen, related only to PCSK9, not the topic of this abstract, Ingiäld Hafström: None declared
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| 32. |
- Ajeganova, S., et al.
(författare)
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Long-term fracture risk in rheumatoid arthritis: impact of early sustained DAS28-remission and restored function, progressive erosive disease, body mass index, autoantibody positivity and glucocorticoids. A cohort study over 10 years
- 2023
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Ingår i: BMC Rheumatology. - 2520-1026. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRisk of fragility fractures in patients with rheumatoid arthritis (RA) is increased. Disease-related inflammation in RA is associated with low Bone Mineral Density (BMD). However, effects of specific disease factors on fracture occurrence and whether or not such disease effects are independent of BMD are unknown.MethodsAnalysis of fracture outcome in the prospective cohort of 2557 patients with early RA (67% women, mean age 58.1 & PLUSMN; 15.6 years) during an observation period of 10.6 & PLUSMN; 4.7 years. In 602 patients BMD was measured at baseline. The first major fragility fractures were considered. Kaplan-Meier and Cox regression analysis, adjusted for traditional factors, prior fracture, disease activity and period of inclusion, were used to estimate the risk of the outcome.ResultsDuring follow-up fracture occurred in 352 patients (13.8%), a rate of 13/1000 p-y. A proportional risk reduction for the outcome was associated with Body Mass Index (BMI) at baseline, BMI & GE; 30 kg/m(2), and over the first two years sustained Disease Activity Score (DAS28)-remission, DAS28-low disease activity and Health Assessment Questionnaire (HAQ) & LE; 0.5. The proportional risk elevation for fractures was associated with BMI & LE; 20 kg/m(2), DAS28 at baseline, 6-month and at 1-year, cumulative DAS28 over the two years, RF, erosion score progression at 2-year, HAQ score and HAQ & GE; 1 at 6-month and 1-year and showed a trend for ACPA positivity. The estimated fracture risk was increased in users of glucocorticoids (GC), associated with a higher GC-dosage at follow-ups and a higher cumulative dosage over two years, independently of disease activity. With adjustment for BMD, there was no difference in fracture outcome by exposure to GC. The effects of a higher BMI, DAS28-remission and low HAQ & LE; 0.5 attained at 6-month of treatment initiation and sustained up to 2 years, RF, ACPA, and erosion score progression at 2-year were independent of low BMD.ConclusionsThis analysis supports importance of RA-specific risk factors in early RA for future major fragility fractures. Treat-to-target strategy and restored functional capacity in early RA-disease are important to prevent fractures. Autoantibody positivity, progressively erosive disease, and low weight could have additional value for personalized fracture preventive strategies in early RA.
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| 36. |
- Ajeganova, S, et al.
(författare)
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Patients with SLE have higher risk of cardiovascular events and mortality in comparison with controls with the same levels of traditional risk factors and intima-media measures, which is related to accumulated disease damage and antiphospholipid syndrome: a case-control study over 10 years
- 2021
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Ingår i: Lupus science & medicine. - : BMJ. - 2053-8790. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- SLE is a strong risk factor for premature cardiovascular (CV) disease and mortality. We investigated which factors could explain poor prognosis in SLE compared with controls.MethodsPatients with SLE and population controls without history of clinical CV events who performed carotid ultrasound examination were recruited for this study. The outcome was incident CV event and death. Event-free survival rates were compared using Kaplan-Meier curves. Relative HR (95% CI) was used to estimate risk of outcome.ResultsPatients (n=99, 87% female), aged 47 (13) years and with a disease duration of 12 (9) years, had mild disease at inclusion, Systemic Lupus Erythematosus Diseases Activity Index score of 3 (1–6) and Systemic Lupus International Collaborating Clinics (SLICC) Damage Index score of 0 (0–1). The controls (n=109, 91% female) were 49 (12) years old. Baseline carotid intima-media thickness (cIMT) did not differ between the groups, but plaques were more prevalent in patients (p=0.068). During 10.1 (9.8-10.2) years, 12 patients and 4 controls reached the outcome (p=0.022). Compared with the controls, the risk of the adverse outcome in patients increased threefold to fourfold taking into account age, gender, history of smoking and diabetes, family history of CV, baseline body mass index, waist circumference, C reactive protein, total cholesterol, high-density lipoprotein, low-density lipoprotein, dyslipidaemia, cIMT and presence of carotid plaque. In patients, higher SLICC score and SLE-antiphospholipid syndrome (SLE-APS) were associated with increased risk of the adverse outcome, with respective HRs of 1.66 (95% CI 1.20 to 2.28) and 9.08 (95% CI 2.71 to 30.5), as was cIMT with an HR of 1.006 (95% CI 1.002 to 1.01). The combination of SLICC and SLE-APS with cIMT significantly improved prediction of the adverse outcome (p<0.001).ConclusionIn patients with mild SLE of more than 10 years duration, there is a threefold to fourfold increased risk of CV events and death compared with persons who do not have SLE with similar pattern of traditional CV risk factors, cIMT and presence of carotid plaque. SLICC, SLE-APS and subclinical atherosclerosis may indicate a group at risk of worse outcome in SLE.
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| 39. |
- Ajeganova, S, et al.
(författare)
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Similar progression of carotid intima-media thickness in 7-year surveillance of patients with mild SLE and controls, but this progression is still promoted by dyslipidaemia, lower HDL levels, hypertension, history of lupus nephritis and a higher prednisolone usage in patients
- 2020
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Ingår i: Lupus science & medicine. - : BMJ. - 2053-8790. ; 7:1, s. e000362-
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Tidskriftsartikel (refereegranskat)abstract
- To compare progression of subclinical atherosclerosis and factors promoting it in patients with SLE and controls.MethodsConsecutive patients with SLE and age-matched, sex-matched population controls from the SLEVIC cohort were assessed at inclusion and after 7 years with standardised data collection and carotid ultrasound. Effect of risk factors on carotid intima–media thickness (cIMT) progression was examined with adjusted linear mixed models.ResultsA total of 77 patients and 74 controls, 68% and 61% of the original cohort, completed follow-up. The patients were (mean) 47 years old, 90% were women, and controls were 51 years old, 92% women. Patients had disease duration of (mean) 11 years, mild disease activity and low severity at both assessments. Baseline cIMT did not differ between the groups. An average absolute cIMT progression was 0.009 mm/year in patients and 0.011 mm/year in controls, intergroup difference p=0.9.Of factors at inclusion, dyslipidaemia, lower levels of high-density lipoprotein (HDL) and carotid plaque in patients and controls, and higher systolic blood pressure, total cholesterol:HDL and LDL:HDL ratios and triglycerides in patients were associated with cIMT progression. Of factors at follow-up, hypertension and blood lipids in patients and HDL in controls were significantly associated with cIMT progression. History of lupus nephritis and a higher average dose of prednisolone used since diagnosis were associated with cIMT progression in patients. Associations of risk factors with cIMT progression were stronger in presence of plaques.ConclusionWe observed a statistically comparable progression of cIMT in patients with mild SLE and controls over 7 years, which implies that progression of subclinical atherosclerosis in some patients with SLE could follow that of the general population. Traditional cardiovascular (CV) risk factors, history of lupus nephritis and higher use of corticosteroids promote cIMT progression in SLE. Detection of carotid plaque may add to CV risk stratification.
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| 41. |
- Ajeganova, S, et al.
(författare)
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TEAM-REHABILITATION BENEFITS BODY COMPOSITION AND FUNCTIONAL OUTCOME BEYOND TIME OF THE REHABILITATION PERIOD IN INFLAMMATORY ARTHRITIS, OF WHICH BODY COMPOSITION IS LINKED TO CHANGE IN LEVEL OF CARDIORESPIRATORY FITNESS, WHEREAS MUSCLE MASS AND STRENGTH ARE LINKED TO PHYSICAL FUNCTIONING
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 1262-1263
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Low physical activity, accumulated disability and disease chronicity contribute to adverse body composition and reduced cardiorespiratory fitness in patients with chronic inflammatory diseases. In the general population, physical exercise improves body composition, muscle strength and aerobic capacity but in inflammatory diseases it is not well established.Objectives:To investigate whether 1) exercise intervention in patients with arthritis affects body composition, physical and aerobic capacity, and whether 2) body composition and physical capacity could explain outcomes as HAQ and aerobic capacity.Methods:Consecutive patients with inflammatory arthritis and a clinical need for rehabilitation, ages 18-80 years, participated in a team-rehabilitation program for 4 weeks. Anthropometry, body composition assessed with bioelectrical impedance analysis, muscle force with hand grip strength and Times sit-to-stand test (TST), activity limitation with the HAQ score and cardiorespiratory fitness with the Åstrand 6-minute cycle test for VO2 max were measured pre-rehabilitation and after 3 and 12 months. The ANOVA model with Bonferroni correction, adjusted for age, sex and baseline measures, was used for the pairwise comparisons of repeated measures overtime. Association between body composition, physical functioning, and the course of HAQ and cardiorespiratory fitness for 12 months was determined with linear mixed models adjusted for age, gender and comorbidity.Results:The study evaluated 149 patients with rheumatoid arthritis (RA), psoriasis arthritis, spondylarthritis and juvenile idiopathic arthritis, aged mean (SD) 53(13) years, 74% women, disease duration 21(13) years, HAQ 1.1(0.6) at inclusion and DAS28 4.1(1.3) for those with RA.There was a statistically significant reduction of BMI between pre-rehabilitation and after 3 months, reduction of waist circumference, body fat, fat mass and the fat mass index after 3 and 12 months, adjusted p<0.05. The muscle mass of total body, arms and legs did not change significantly post-rehabilitation compared to pre-rehabilitation. Hand grip strength and TST improved together with reduction of HAQ and increased VO2 max after 3 and 12 months, adjusted p<0.05 adjusted for age, sex and baseline measures.The HAQ overtime was independently associated with total body muscle mass, legs muscle mass, hand grip strength, and TST pre-rehabilitation, but not to the change of body composition overtime.The course of VO2 max overtime was independently associated with pre-rehabilitation BMI, waist circumference, muscle mass of total body, arms and legs, fat mass, body fat, the fat mass index and TST, as well as with change of BMI, waist circumference, fat mass and the fat mass index between pre-rehabilitation and after 3 and 12 months.Conclusion:We observed benefits of intervention with a team-rehabilitation program for 4 weeks on body composition profile, functioning, physical limitation and cardiorespiratory fitness, which were presented beyond the time of the rehabilitation period for up to 12 months. Different aspects of body composition and physical capacity were associated with levels of disability measured with HAQ and with cardiorespiratory fitness. This study indicates that in patients with inflammatory arthritis, muscle mass and strength were linked to HAQ over time, whereas the measures of body composition could be more linked to cardiorespiratory fitness than to HAQ.Disclosure of Interests:None declared
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| 42. |
- Ajeganova, S, et al.
(författare)
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Team Rehabilitation in Inflammatory Arthritis Benefits Functional Outcomes Along With Improved Body Composition Associated With Improved Cardiorespiratory Fitness
- 2021
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Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 48:9, s. 1371-1378
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the effect of team rehabilitation in inflammatory arthritis (IA) on body composition and physical function. Further, we examined whether body composition and physical function are associated with disability and cardiorespiratory fitness (CRF).MethodsThe participants were 149 patients (74% women) with chronic arthritis, a mean age of 53 (SD 13) years, and mean disease duration of 21 (SD 13) years. They participated in a 4-week team rehabilitation program and were evaluated at prerehabilitation, and at 3 and 12 months postrehabilitation. Body composition was assessed by bioelectrical impedance analysis and CRF by the Åstrand 6-minute cycle test. ANCOVA with Bonferroni correction and linear mixed models were applied.ResultsAfter 3 and 12 months, there were significant reductions in waist circumference and measures of fat, adjusted for age, sex, and baseline measures. The prevalence of adiposity and central obesity decreased after 12 months. Hand grip strength and timed sit-to-stand (TST) improved together with reduction in Health Assessment Questionnaire (HAQ) and increased VO2max after 3 and 12 months. HAQ reduction over time was associated with prerehabilitation measures of lean mass of legs, hand grip strength, TST, and physical activity, and changes in hand grip strength, physical activity, and sedentary time, but not with changes of body composition. VO2max improvement over time was associated with prerehabilitation BMI, waist circumference, measures of fat and lean mass, changes in BMI, waist circumference, and measures of fat.ConclusionIn patients with IA, 4-week team rehabilitation benefited body composition, level of physical functioning, activity, and CRF for up to 12 months. Measures of physical function and activity were linked to HAQ over time, whereas body composition was linked to CRF.
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| 43. |
- Ajeganova, S., et al.
(författare)
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The association between anti-carbamylated protein (anti-CarP) antibodies and radiographic progression in early rheumatoid arthritis : A study exploring replication and the added value to ACPA and rheumatoid factor
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:1, s. 112-118
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Tidskriftsartikel (refereegranskat)abstract
- Objective Anti-carbamylated protein (anti-CarP) antibodies are reported to associate with more radiographic progression within the total rheumatoid arthritis (RA) population and anti-citrullinated peptide antibody (ACPA)-negative subgroup. We explored the association of anti-CarP with radiographic progression in RA and aimed to replicate the association and evaluate the added value of anti-CarP antibodies in relation to ACPA and rheumatoid factor (RF). Methods 576 Swedish and 628 Dutch patients with RA (2394 and 3247 sets of radiographs, respectively) were longitudinally studied. Replication was restricted to the Swedish patients. In both cohorts, the association of anti-CarP with radiographic progression was determined in strata of patients with similar ACPA and RF status; results of both cohorts were combined in fixed-effect meta-analyses. The net percentage of patients for whom the radiographic progression in 5 years was additionally correctly classified when adding anti-CarP to a model including ACPA and RF was evaluated. Results Anti-CarP associated with radiographic progression in the total Swedish RA population (beta=1.11 per year, p=8.75×10-13) and in the ACPAnegative subgroup (beta=1.14 per year, p=0.034). Anti- CarP associated with more radiographic progression in the strata of ACPA-positive/RF-negative, ACPA-negative/ RF-positive and ACPA-positive/RF-positive patients with RA (respective p values 0.014, 0.019 and 0.0056). A model including ACPA and RF correctly classified 54% and 57% of the patients; adding anti-CarP to this model did not increase these percentages (54% and 56% were correctly classified). Conclusions Anti-CarP antibodies associated with more severe radiographic progression in the total and ACPA-negative RA population. Anti-CarP-positivity had a statistically significant additive value to ACPA and RF, but did not improve correct classification of patients.
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| 44. |
- Derksen, V. F A M, et al.
(författare)
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Rheumatoid arthritis phenotype at presentation differs depending on the number of autoantibodies present
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76, s. 716-720
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Tidskriftsartikel (refereegranskat)abstract
- Objectives In rheumatoid arthritis (RA), seropositive and seronegative disease may be two entities with different underlying pathophysiological mechanisms, long-term outcomes and disease presentations. However, the effect of the conjoint presence of multiple autoantibodies, as proxy for a more pronounced humoral autoimmune response, on clinical phenotype remains unclear. Therefore, this study investigates the association between the number of autoantibodies and initial clinical presentation in two independent cohorts of patients with early RA. Methods Autoantibody status (rheumatoid factor, anticitrullinated protein antibodies and anticarbamylated protein antibodies) was determined at baseline in the Leiden Early Arthritis Cohort (n=828) and the Swedish BARFOT (Better Anti-Rheumatic Farmaco-Therapy, n=802) study. The association between the number of autoantibodies and baseline clinical characteristics was investigated using univariable and multivariable ordinal regression. Results In both cohorts, the following independent associations were found in multivariable analysis: patients with a higher number of RA-associated antibodies were younger, more often smokers, had a longer symptom duration and a higher erythrocyte sedimentation rate at presentation compared with patients with few autoantibodies. Conclusions The number of autoantibodies, reflecting the breadth of the humoral autoimmune response, is associated with the clinical presentation of RA. Predisease pathophysiology is thus reflected by the initial clinical phenotype.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Frostegård, J., et al.
(författare)
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Autoantibody profiling reveals four protein candidate autoantigens associated with systemic lupus erythematosus
- 2018
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Ingår i: Lupus. - : SAGE PUBLICATIONS LTD. - 0961-2033 .- 1477-0962. ; 27:10, s. 1670-1678
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Tidskriftsartikel (refereegranskat)abstract
- Objectives In systemic lupus erythematosus (SLE) there are typically many autoantibodies. The disease heterogeneity could be better understood with discovery of phenotype-specific antigens targeted by autoantibodies. We here aimed to identify novel autoantigens potentially related to SLE disease and a major complication, atherosclerosis. Methods Antigen microarrays were used to profile IgG autoantibody reactivity against 77 protein fragments (20-140 amino acids (aa) long, median 89 aa) produced within the Human Protein Atlas project, in serum samples from SLE patients (n=107) and age- and sex-matched population-based controls (n=107). Common carotid intima-media thickness, plaque occurrence and echogenicity were determined by B-mode ultrasound. Results We determined significant differences between patients and controls in IgG reactivity against four proteins. In patients compared to controls, there was an increase of IgG reactivity against zinc finger protein 688 (ZNF688), early B cell factor 2 (EBF2), crystallin, alpha B (CRYAB) and tumor necrosis factor receptor superfamily member 13C (TNFRSF13C). Of these four antigens, only anti-ZNF688 was associated with carotid atherosclerosis (plaque occurrence) and vulnerable plaques in SLE. There was a weak association between anti-EBF2 and SLE disease activity but no significant associations were determined for other measured IgG reactivity. Conclusions In this discovery screening we here demonstrate new candidate autoantigens with differential reactivity (reflecting autoantibody levels) in SLE patients and in controls and in relation to atherosclerosis in SLE.
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| 49. |
- Leu Agelii, Monica, 1977, et al.
(författare)
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Misdiagnosis of Rheumatoid Arthritis in a Long-Term Cohort of Early Arthritis Based on the ACR-1987 Classification Criteria
- 2022
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Ingår i: Open Access Rheumatology-Research and Reviews. - 1179-156X. ; 14, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Correct diagnosis of early rheumatoid arthritis (RA) is essential for optimal treatment choices. No pathognomonic test is available, and diagnosis is based on classification criteria, which can result in misdiagnosis. Here, we examined the differences between actual and misdiagnosed RA cases in a long-term cohort of patients included based on the ACR-1987 classification criteria.Methods: Patients in the BARFOT (Better Anti-Rheumatic PharmacOTherapy) cohort (n=2543) with at least four follow-up visits during the initial 5 years from enrolment were assessed, and a change in diagnosis was reported by the treating rheumatologist. The groups were analysed with respect to the individual classification criteria, antibodies to citrullinated proteins (ACPA), disease activity (DAS28) and radiographic changes from inclusion up to 2 years.Results: Forty-five patients (1.8%) were misdiagnosed (RA-change group). When compared to those in the RA-change group, the patients who kept their diagnosis (RA-keep) were more often RF positive (64% vs 21%, p<0.001) or ACPA positive (59% vs 8%, p<0.001). They were also more likely to fulfil more than four ACR-1987 criteria (64% vs 33%, p<0.001) and to have radiographic changes at inclusion (RA-keep 27% vs RA-change 12%, p=0.04). The groups had a similar evolution of DAS28 and its components as well as of radiological joint destruction.Conclusion: Diagnosis of RA according to the ACR-1987 criteria had a high precision in this long-term cohort. A diagnosis of RA should be re-evaluated in patients who do not fulfil more than four ACR-1987 criteria especially in patients negative for RF.
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- Liu, A, et al.
(författare)
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PCSK9 IS ASSOCIATED WITH DISEASE ACTIVITY AND IMPLICATED IN IMMUNE ACTIVATION IN SYSTEMIC LUPUS ERYTHEMATOSUS
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 1361-1362
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- LDL-levels are increased by Proprotein convertase subtilisin kexin 9 (PCSK9) which targets the LDL-receptor (LDLR). We reported that PCSK9 has immune modulatory properties in addition to LDL-lowering and ameliorates dendritic cell (DC) activation by oxidized LDL (OxLDL)1, which is abundant in atherosclerotic plaques. OxLDL is also raised and associated with cardiovascular disease (CVD) in SLE.1-3Objectives:We here investigate the role of PCSK9 in SLE both in a clinical context and in experimental ex vivo studies. The objective is to investigate if PCSK9 and its inhibition could be of relevance in SLE in addition to LDL-level related propertiesMethods:PCSK9-levels were determined by ELISA among SLE patients (n=109) and age- and sex-matched population-based controls (n=91). Common carotid intima-media thickness (IMT) and plaque occurrence were determined by B-mode ultrasound. Plaques were graded by echogenicity. Human peripheral blood monocytes from SLE patients or controls were differentiated into DCs. Effects of PCSK9 and its inhibition by silencing were studied.Results:PCSK9-levels were non-significantly higher among SLE-patients as compared to controls but associated significantly with SLE disease activity, as determined by SLAM (0.020) or SLEDAI (0.0178). There was no association between PCSK9-levels and atherosclerosis as determined by IMT, prevalence of plaques or echolucent (potentially vulnerable) plaques. PCSK9 levels were significantly associated with CVD among SLE-patients but not after adjustment for age.OxLDL induced PCSK9 in DCs and DC-maturation with increased expression of CD86 and HLA-DR. The effects were significantly stronger in DC from SLE patients than from controls. Silencing of PCSK9 abolished OxLDL-induced DC-maturation.Conclusion:PCSK9 is associated with disease activity in SLE. One underlying cause could be OxLDL, promoting DC-activation which depends on PCSK9. OxLDL induces PCSK9, an effect which is higher among SLE-patients.PCSK9 could play an unexpected immunological role in SLE and inhibition of PCSK9 could potentially play a role in disease amelioration, pending on clinical studies.References:[1]Liu A and Frostegard J. PCSK9 plays a novel immunological role in oxidized LDL-induced dendritic cell maturation and activation of T cells from human blood and atherosclerotic plaque.J Intern Med. 2018.[2]Frostegard J, Svenungsson E, Wu R, Gunnarsson I, Lundberg IE, Klareskog L, Horkko S and Witztum JL. Lipid peroxidation is enhanced in patients with systemic lupus erythematosus and is associated with arterial and renal disease manifestations.Arthritis Rheum. 2005;52:192-200.[3]Frostegard J. Immunity, atherosclerosis and cardiovascular disease.BMC Med. 2013;11:117.Disclosure of Interests:Anquan Liu: None declared, Mizanur Rahman: None declared, Ingiäld Hafström: None declared, Sofia Ajeganova: None declared, Johan Frostegård Grant/research support from: Unconditional competitive grant from Amgen, related only to PCSK9, not the topic of this abstract
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