| 10111. |
- Andersson, Maria L.E., et al.
(author)
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Autoantibodies to Disease-Related Proteins in Joints as Novel Biomarkers for the Diagnosis of Rheumatoid Arthritis
- 2023
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In: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:7, s. 1110-1119
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Journal article (peer-reviewed)abstract
- Objective. This study was undertaken to develop and characterize a multiplex immunoassay for detection of autoantibodies against peptides derived from proteins known to play a role in development of arthritis and that are also expressed in joints.Methods. We selected peptides from the human counterpart of proteins expressed in the joints, based on mouse models that showed these to be targeted by pathogenic or regulatory antibodies in vivo. Using bead-based flow immunoassays measuring IgG antibodies, we selected triple helical or cyclic peptides, containing the epitopes, to avoid collinear reactivity. We characterized the analytical performance of the immunoassay and then validated it in 3 independent rheumatoid arthritis (RA) cohorts (n = 2,110), Swedish age- and sex-matched healthy controls, and patients with osteoarthritis (OA), patients with psoriatic arthritis (PsA), and patients with systemic lupus erythematosus (SLE).Results. Screening assays showed 5 peptide antigens that discriminated RA patients from healthy controls with 99% specificity (95% confidence interval [CI] 98-100%). In our validation studies, we reproduced the discriminatory capacity of the autoantibodies in 2 other RA cohorts, showing that the autoantibodies had high discriminatory capacity for RA versus OA, PsA, and SLE. The novel biomarkers identified 22.5% (95% CI 19-26%) of early RA patients seronegative for anti-cyclic citrullinated peptide and rheumatoid factor. The usefulness of the biomarkers in identifying seronegative RA patients was confirmed in validation studies using 2 independent cohorts of RA patients and cohorts of patients with OA, PsA, and SLE.Conclusion. A multiplex immunoassay with peptides from disease-related proteins in joints was found to be useful for detection of specific autoantibodies in RA serum. Of note, this immunoassay had high discriminatory capacity for early seronegative RA.
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| 10112. |
- Andersson, Maria L.E. 1968-, et al.
(author)
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Baseline levels of circulating galectin-1 associated with radiographic hand but not radiographic knee osteoarthritis at a two-year follow-up
- 2024
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In: OSTEOARTHRITIS AND CARTILAGE OPEN. - Oxford : Elsevier. - 2665-9131. ; 6:2
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Journal article (peer-reviewed)abstract
- Objective: We tested the potential of circulating galectin-1, interleukin (IL)-1 beta, IL-6, and tumour necrosis factor alpha (TNF alpha) levels at baseline in individuals with knee pain as biomarkers for development of radiographic knee and/or hand osteoarthritis (OA). Design:This study comprised 212 individuals with knee pain from the Halland osteoarthritis cohort (HALLOA). Clinical characteristics and serum/plasma levels of galectin-1, IL-1 beta, IL-6, and TNF alpha were measured at baseline, and knee and hand radiographs were obtained at a two-year follow-up. The predictive value of circulating inflammatory markers and clinical variables at baseline was assessed using multinominal logistic regression for those who developed radiographic OA in knees only (n = 25), in hands only (n = 40), and in both knees and hands (n = 43); the group who did not develop OA (n = 104) was used as reference. Correlations were assessed using Spearman's correlation coefficients. Results: As expected, age was identified as a risk factor for having radiographic knee and/or hand OA at the twoyear follow-up. Baseline circulating galectin-1 levels did not associate with developing radiographic knee OA but associated with developing radiographic hand OA (odds ratio (OR) for a 20% increased risk: 1.14, 95% confidence interval (CI) 1.01-1.29) and both radiographic knee and hand OA (OR for a 20% increased risk: 1.18, 95% CI 1.05-1.30). However, baseline IL-1 beta, IL-6, and TNF alpha did not associate with developing radiographic knee and/or hand OA. Conclusion: Non-age adjusted circulating galectin-1 is superior to IL-6, IL-1 beta, and TNF alpha in predicting radiographic hand but not knee OA.
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| 10113. |
- Andersson, Maria L.E., et al.
(author)
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Cohort profile: the Halland osteoarthritis (HALLOA) cohort-from knee pain to osteoarthritis: a longitudinal observational study in Sweden
- 2022
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In: Bmj Open. - London : BMJ. - 2044-6055. ; 12:7
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Journal article (peer-reviewed)abstract
- Purpose The overall objective in this study is to investigate the early development of radiographic knee osteoarthritis (OA) and its association with hand or/and knee OA, metabolic diseases, biomarkers, chronic pain, physical function and daily physical activity types. Participants The Halland osteoarthritis (HALLOA) cohort is a longitudinal cohort study that includes individuals with knee pain in the southwest of Sweden. Enrolment took place from 2017 to 2019. The inclusion criteria were current knee pain, with no former known radiographic knee OA and no cruciate ligament rupture or rheumatological disorder. The participants were recruited: (1) when seeking care for knee pain in primary healthcare or (2) by advertisements in local newspapers. There are 306 individuals included in the study, mean age (SD) 51.7 (8.7) years and 69% are women. The baseline and follow-ups include clinical tests, radiographical examinations, blood samples, metabolic measures, pain pressure thresholds, tests of physical functions, daily physical activity types and patient-reported outcomes. Findings to date There were associations between metabolic factors and radiographic knee OA, even in those with normal body mass index at baseline. In addition, clinical hand OA was positively associated with fasting plasma glucose. We also found that modifiable factors as increased visceral fat and total body fat were associated with increased pain sensitivity among individuals with knee pain. Future plans By studying possible pathophysiological mechanisms of OA over time, we aim to provide new insights on OA progression, identify usable preventive measures helping the clinicians in the management of the disease and improve health for the patients. It is also important to study the development of chronic pain in OA, to get tools to identify individuals at risk and to be able to offer them treatment.
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| 10114. |
- Andersson, M. L. E., et al.
(author)
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Diurnal variation in serum levels of cartilage oligomeric matrix protein in patients with knee osteoarthritis or rheumatoid arthritis
- 2006
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 65:11, s. 1490-1494
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Journal article (peer-reviewed)abstract
- Objective: To monitor changes in serum concentrations of cartilage oligomeric matrix protein (COMP) during a 24-h period to determine any diurnal variation, and to estimate the half life of COMP in the circulation in patients with symptomatic knee osteoarthritis and in those with rheumatoid arthritis. Methods: Serum samples were drawn every 4 h (7 samples/patient over 24 h) in 10 patients with knee osteoarthritis and 14 patients with rheumatoid arthritis. Osteoarthritis was defined radiographically and clinically (American College of Rheumatology (ACR) criteria) and rheumatoid arthritis according to the 1987 ACR criteria. Serum COMP was measured by sandwich ELISA. A statistical model for the diurnal variation in the COMP levels was developed using the computer program NONMEM. Results: No considerable changes in COMP levels were observed during the day between 08:00 and 21:00 in either group. A significant decrease in serum COMP was apparent during bed rest at night, reaching the lowest levels between 04:00 and 05:00 (p < 0.03 or better v all other time points) in patients with osteoarthritis and in those with rheumatoid arthritis. From the rate of decreasing serum COMP levels, a putative half life of COMP in the circulation was estimated to be 7.4 h. Conclusion: During normal daytime activities, serum COMP levels are constant. The decrease during the night indicates a rapid elimination of COMP once it has reached the circulation. The stable COMP levels during the day suggest that it is not necessary to further standardise the time of serum sampling in clinical practice.
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| 10115. |
- Andersson, Maria L. E., et al.
(author)
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Early increase in serum-COMP is associated with joint damage progression over the first five years in patients with rheumatoid arthritis
- 2013
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In: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 14
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Journal article (peer-reviewed)abstract
- Background: Currently available biomarkers for the early tissue process leading to joint damage in rheumatoid arthritis are insufficient and lack prognostic accuracy, possibly a result of variable activity of the disease over time. This study represents a novel approach to detect an altered activity of the disease process detected as increasing serum-COMP levels over a short time and whether this would correlate with joint damage progression over the first 5 years of disease. Methods: In all, 349 patients from the Swedish BARFOT early RA study were examined. Serum-COMP was analysed by ELISA at diagnosis and after 3 months. Based on changes in serum-COMP levels, three subgroups of patients were defined: those with unchanged levels (change <= 20%) (N=142), decreasing levels (> 20%) (N=173) and increasing levels (> 20%) (N=34). Radiographs of hands and feet were obtained at inclusion, after 1, 2 and 5 years and scored according to Sharp van der Heijde (SHS). Radiographic progression was defined as increase in SHS by >= 5.8. Results: The group of patients with increasing COMP levels showed higher median change in total SHS and erosion scores at 1, 2 and 5 year follow-up compared with the groups with stable or decreasing COMP levels. Furthermore, the odds ratio of radiographic progression was 2.8 (95% CI 1.26-6.38) for patients with increasing COMP levels vs. patients with unchanged levels. The group of patients with increasing COMP levels had higher ESR at inclusion but there were no baseline differences between the groups for age, gender, disease duration, disease activity (DAS28), function (HAQ), CRP, nor presence of rheumatoid factor or anti-CCP. Importantly, neither did changes over the 3-month period in DAS28, HAQ, ESR nor CRP differ between the groups and these variables did not correlate to joint damage progression. Conclusion: Increasing serum-COMP levels between diagnosis and the subsequent 3 months in patients with early RA represents a novel indicator of an activated destructive process in the joint and is a promising tool to identify patients with significant joint damage progression during a 5-year period.
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| 10116. |
- Andersson, M. L.E., et al.
(author)
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Pain in rheumatoid arthritis: a seven-year follow-up study of pain distribution and factors associated with transition from and to chronic widespread pain
- 2022
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In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; :51, s. 345-354
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Journal article (peer-reviewed)abstract
- Objective: To study transitions from and to chronic widespread pain (CWP) over 7 years in patients with rheumatoid arthritis (RA). Method: Two postal questionnaires were sent to patients included in the BARFOT (Better Anti-Rheumatic Pharmacotherapy) study, the first in 2010 and the second in 2017. The questionnaires assessed pain, number of tender and swollen joints, functional disability, health-related quality of life (HRQoL), pharmacological treatment, lifestyle factors, and patient-reported body mass index (BMI). The responders to both questionnaires were divided into three groups according to the reported pain duration and distribution: patients having no chronic pain (NCP), chronic regional pain (CRP), and CWP. Results: In all, 953 patients answered the questionnaires at both time-points. One-third (324) of the patients reported CWP in 2010, and 140 (43%) of the patients had transition to NCP or CRP in 2017. In multivariate logistic regression models, adjusting for age, gender, and disease duration, transition from CWP was associated with normal BMI, fewer tender joints, less pain, less fatigue, fewer pain regions, less disability, better HRQoL, and biologic treatment. In 2010, 628 patients reported NCP or CRP, whereas 114 of them reported CWP in 2017. Transition to CWP was associated with female gender, obesity, more tender and swollen joints, higher pain-related variables, worse disability, and worse HRQoL. Conclusion: There are modifiable factors associated with transitions from and to CWP that could be identified. Paying attention to these factors could improve pain treatment in the management of RA.
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| 10117. |
- Andersson, Maria L.E., et al.
(author)
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Patients with early rheumatoid arthritis in the 2000s have equal disability and pain despite less disease activity compared with the 1990s : Data from the barfot study over 8 years
- 2017
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In: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 44:6, s. 723-731
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Journal article (peer-reviewed)abstract
- Objective. To compare outcomes over the first 8 years in patients with early rheumatoid arthritis (RA) recruited in the 1990s and the 2000s, with a special focus on functional disability and its possible predictors. Methods. Data were acquired from 1938 patients with early RA (American College of Rheumatology 1987 criteria) included in the BARFOT study, who had completed the 8-year followup. The patients were divided into 2 cohorts: cohort 1 (n = 928, 68% women) included from 1992 to 1999 and cohort 2 (n = 1010, 70% women) included from 2000 to 2006. Health Assessment Questionnaire (HAQ), 28-joint Disease Activity Score (DAS28), visual analog scale pain, and radiographs of hands and feet scored by the van der Heijde modified Sharp method were assessed during the 8 years. Longitudinal data analyses were performed using a generalized linear model. Results. Despite more active medical treatment during the 2000s, the courses of HAQ and pain showed no difference between the cohorts during followup, in either women or in men, with significantly higher levels in women compared with men. However, as expected, disease activity decreased more over time in cohort 2 compared with cohort 1, for both sexes, and women in cohort 2 had less radiographic progression compared with cohort 1. HAQ was associated with DAS28, pain, radiological scores, and sex in both cohorts, and in cohort 2 also with age and smoking. Conclusion. Patients included in the 2000s had lower disease activity, but not less activity limitation and pain over 8 years of followup despite more active treatment. Pain, aging, and smoking might explain why patients included in the 2000s still had the same disability levels as those included in the 1990s.
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| 10118. |
- Andersson, Marie-Louise
(author)
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Human Endogenous Retroviruses: Expression and Evolutionary Relationships
- 2001
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Doctoral thesis (other academic/artistic)abstract
- The human genome contains genetic elements which are more or less similar to infectious retroviruses. These are called human endogenous retroviruses (HERVs) and are thought to be remnants of infections in the primate lineage. Most of them have been inserted 10 to 60 million years ago but have at different time points spread in the genome via intracellular retrotransposition and make up as much as 7 % of the human genome. It is not known whether these elements have any biological function or are involved in any disease. The thousands of HERV elements in the human genome have been divided into class I, II and III elements according to their similarities to different exogenous retroviruses. We have in this thesis been working with class II HERVs. Elements in this class have similarities to type A, B, D and avian type C retroviruses. We have classified these elements into ten groups. We have also shown that one of these groups, HML-1, was integrated into the genome 30 to 45 million years ago, while another class II group, HML-3 was present in a few copies more than 45 million years ago and subsequently expanded in the genome of the Old World monkey/hominoid lineage. Yet another group, members of the HML-5 group were present in multiple copies at least 45 million years ago and may be the oldest class II HERVs. We have in this thesis also shown that the class II elements have a heterogenous expression among individuals in several cell types. This suggests that these elements have retained regulatory elements in their LTRs. We have also shown, by studying the dbEST libraries, that HERV-K(HML-2) is the only class II group with a high expression in human tissues. HML-1, HML-3, HML-5, HERV-K(HML-6) and HERV-K(C4) were expressed in several tissues but to a lower extent. No expression was detected for HML-4 and HML-7 to HML-9.
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| 10119. |
- Andersson, Matilda L., et al.
(author)
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Linking behavioural type with cannibalism in Eurasian perch
- 2021
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In: PLOS ONE. - : Public Library Science. - 1932-6203. ; 16:12
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Journal article (peer-reviewed)abstract
- The propensity to kill and consume conspecifics (cannibalism) varies greatly between and within species, but the underlying mechanisms behind this variation remain poorly understood. A rich literature has documented that consistent behavioural variation is ubiquitous across the animal kingdom. Such inter-individual behavioural differences, sometimes referred to as personality traits, may have far-reaching ecological consequences. However, the link between predator personality traits and the propensity to engage in cannibalistic interactions remains understudied. Here, we first quantified personality in Eurasian perch (Perca fluviatilis), measured as activity (time spent moving) and sociability (time spent near conspecifics). We then gave perch of contrasting behavioural types the option to consume either conspecific or heterospecific (roach, Rutilus rutilus) prey. Individual perch characterized by a social-active behavioural phenotype (n = 5) selected roach before being cannibalistic, while asocial-inactive perch (n = 17) consumed conspecific and heterospecific prey evenly. Thus, asocial-inactive perch expressed significantly higher rates of cannibalism as compared to social-active individuals. Individual variation in cannibalism, linked to behavioural type, adds important mechanistic understanding to complex population and community dynamics, and also provides insight into the diversity and maintenance of animal personality.
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| 10120. |
- Andersson, Maria LE, et al.
(author)
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The Effect of Stopping Smoking on Disease Activity in Rheumatoid Arthritis (RA). Data from BARFOT, a Multicenter Study of Early RA
- 2012
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In: Open Rheumatology Journal. - : Bentham Science Publishers Ltd.. - 1874-3129. ; 6, s. 303-309
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Journal article (peer-reviewed)abstract
- OBJECTIVE: We studied the effect of stopping smoking on disease activity in patients with RA.METHODS: Between 1992 and 2005, 2,800 adult patients were included in the BARFOT early RA study in Sweden. Disease Activity Score 28 joints (DAS28), C-reactive protein (CRP), Health Assessment Questionnaire (HAQ), rheumatoid factor (RF), anti-CCP, general health and pain visual analog scales (VAS), EULAR response and treatment were registered at inclusion and at follow-up 2, 5 and 8 years. In 2010, a self-completion postal questionnaire was sent to 2,102 patients, enquiring about lifestyle factors, including cessation of smoking.RESULTS: A total of 1,460 adult RA patients with disease duration ≤2 years were included in this study. Seventeen percent smoked in 2010. In total, 127 patients stopped smoking after inclusion in the study. Smoking cessation after inclusion in the study was negatively associated with EULAR good outcome at 8 years (OR 0.44, 95% CI 0.22-0.86, p=0.02), controlled for age, disease duration, sex, socioeconomic class, smoking status, RF, and DAS28 at inclusion.CONCLUSION: Seventeen percent of the RA patients smoked in 2010 in this large Swedish RA cohort. Stopping smoking after onset of RA did not change the poor prognosis of smokers with RA, but all RA patients need to stop smoking because of the high risk of cardiovascular mortality and morbidity and the association of smoking with vasculitis and noduli in RA.
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