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- Pertsinidou, Eleftheria, et al.
(författare)
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In early rheumatoid arthritis, anticitrullinated peptide antibodies associate with low number of affected joints and rheumatoid factor associates with systemic inflammation
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 83:3, s. 277-287
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate how individual rheumatoid arthritis (RA) autoantibodies associate with individual signs and symptoms at the time of RA diagnosis.Methods: IgA, IgG, IgM rheumatoid factor (RF), antibodies against cyclic citrullinated peptide version 2 (anti-CCP2) and 16 individual antibodies against citrullinated protein (ACPA) reactivities were analysed centrally in baseline sera from 1600 patients with RA classified according to the 1987 American College of Rheumatology (ACR) criteria. These results were related to C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), number of swollen and tender joints (SJC and TJC), 28-joint disease activity scores (DAS28 and DAS28CRP), global disease activity evaluated by the patients and Health Assessment Questionnaire, all obtained at baseline.Results: Individually, all autoantibodies except immunoglobulin G (IgG) RF associated with low SJC and TJC and with high ESR. In IgM RF-negative patients, ACPA associated strictly with low number of swollen and tender joints. This association persisted in multiple regression and stratified analyses where IgM and IgA RF instead associated with inflammation expressed as ESR. Among subjects without any ACPA peptide reactivity, there was no association between RF isotypes and ESR. The effect of RF on ESR increased with the number of ACPA reactivities, especially for IgM RF. In patients fulfilling the 1987 ACR criteria without taking RF into account, associations between IgM RF and high ESR, as well as between ACPA and low joint counts, remained.Conclusion: Whereas ACPA associate with low counts of affected joints in early RA, RF associates with elevated measures of systemic inflammation in an ACPA-dependent manner. This latter finding corroborates in vitro models of ACPA and RF in immune complex-induced inflammation. These phenotypic associations are independent of classification criteria.
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- Westerlind, Helga, et al.
(författare)
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Anti-Citrullinated Protein Antibody Specificities, Rheumatoid Factor Isotypes, and Incident Cardiovascular Events in Patients With Rheumatoid Arthritis
- 2020
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Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 72:10, s. 1658-1667
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the relationship between anti–citrullinated protein antibodies (ACPAs), specific ACPA subspecificities, rheumatoid factor (RF) isotypes, and incident cardiovascular (CV) events in patients with rheumatoid arthritis (RA).Methods Serum samples from Swedish patients with new-onset RA (diagnosed within 1 year of symptom onset between 1996 and 2009) were centrally typed for anti–cyclic citrullinated peptide 2 (anti-CCP2) antibodies, 20 ACPA subspecificities, and RF isotypes. Patients were followed up longitudinally in nationwide registers to monitor the occurrence of acute coronary syndrome (ACS), stroke, CV-related death, and major adverse CV events (MACE). The association between each serologic marker and CV outcome, and the impact of adjustment for the Disease Activity Score in 28 joints (DAS28), smoking status, and income at baseline, were assessed using Cox proportional hazards models. In addition, associations of serologic markers with all-cause mortality were explored.Results In total, 2,814 patients with RA were included in the study. The median follow-up was 13 years, during which the CV end points of ACS, stroke, or CV-related death were reported to occur in 375 patients. Occurrence and/or levels of anti-CCP2 were associated with risk of incident ACS (hazard ratio [HR] 1.46, 95% confidence interval [95% CI] 1.03–2.06), stroke (HR 1.47, 95% CI 1.03–2.10), CV-related death (P = 0.024 for association with anti-CCP2 levels), and MACE (HR 1.34, 95% CI 1.06–1.70). Similarly, an association with the number of ACPA subspecificities was observed; however, this could not be attributed to any individual or group of ACPA subspecificities. Presence of IgM-RF was associated with all CV end points except ACS, and IgA-RF was exclusively associated with CV-related death. Adjustment for smoking status, income, and DAS28 scores decreased most of the HRs, whereas IgA-RF remained associated with CV-related death (HR 1.61, 95% CI 1.05–2.48). All of the assessed serologic makers were associated with all-cause mortality.Conclusion RF isotypes and ACPAs are associated with future CV events in patients with RA. ACPA levels and number of subspecificities seem more important than the occurrence of particular subspecificities, and these associations were not explained by a history of ever smoking.
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- Ytterberg, A Jimmy, et al.
(författare)
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Shared immunological targets in the lungs and joints of patients with rheumatoid arthritis : identification and validation
- 2015
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 74:9, s. 1772-1777
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Immunological events in the lungs might trigger production of anti-citrullinated protein antibodies during early rheumatoid arthritis (RA). We investigated the presence of shared immunological citrullinated targets in joints and lungs of patients with RA.PATIENTS AND METHODS: Proteins extracted from bronchial (n=6) and synovial (n=7) biopsy specimens from patients with RA were investigated by mass spectrometry-based proteomics. One candidate peptide was synthesised and used to investigate by ELISA the presence of antibodies in patients with RA (n=393), healthy controls (n=152) and disease controls (n=236). HLA-DRB1 shared epitope (SE) alleles were detected in patients with RA.RESULTS: Ten citrullinated peptides belonging to seven proteins were identified, with two peptides shared between the synovial and bronchial biopsy samples. Further analysis, using accurate mass and retention time, enabled detection of eight citrullinated peptides in synovial and seven in bronchial biopsy specimens, with five peptides shared between the synovial and bronchial biopsy specimens. Two citrullinated vimentin (cit-vim) peptides were detected in the majority of synovial and lung tissues. Antibodies to a synthesised cit-vim peptide candidate (covering both cit-vim peptides identified in vivo) were present in 1.8% of healthy controls, 15% of patients with RA, and 3.4% of disease controls. Antibodies to cit-vim peptide were associated with the presence of the SE alleles in RA.CONCLUSIONS: Identical citrullinated peptides are present in bronchial and synovial tissues, which may be used as immunological targets for antibodies of patients with RA. The data provide further support for a link between lungs and joints in RA and identify potential targets for immunity that may mediate this link.
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- Bonde, J. P. E., et al.
(författare)
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Occupational risk of COVID-19 across pandemic waves: a two-year national follow-up study of hospital admissions
- 2022
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Ingår i: Scandinavian Journal of Work Environment & Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 48:8, s. 672-677
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Tidskriftsartikel (refereegranskat)abstract
- Objective Assuming that preventive measures to mitigate viral transmission of SARS-CoV-2 at the workplace may have been improved in the course of the COVID-19 pandemic, we examined the occupational risk of COVID-19 related hospital admission across the four pandemic waves in Denmark between week 8, 2020, and week 50, 2021. Methods The study included 4416 cases of COVID-19 related hospital admissions among 2.4 million Danish employees aged 20-69 with follow-up in 2020 through 2021. At-risk industrial sectors and a reference population were defined a priory by a job-exposure matrix on occupational risk for COVID-19. Incidence rate ratios (IRR) and potential effect modification by pandemic wave were computed with Poisson regression adjusted for demographic, social and health factors including completed COVID-19 vaccination. Results We observed an overall elevated relative risk in four of six at-risk industrial sectors, but the pandemic wave only modified the risk among healthcare employees, where the excess risk from a high initial level declined to background levels during the latest waves in models not adjusting for COVID-19 vaccination. In social care, education and transport, the elevated risk was not modified by pandemic wave. Conclusion Danish healthcare employees were to some extent protected against occupational transmission of SARS-CoV-2 during the two last pandemic waves even though the absolute risk conferred by occupation may not have been eliminated. Early vaccination of this group seems not to be the only explanation. The risk in other sectors remained elevated indicating a need to revisit preventive measures.
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- Brink, Mikael, et al.
(författare)
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Multiplex Analyses of Antibodies Against Citrullinated Peptides in Individuals Prior to Development of Rheumatoid Arthritis
- 2013
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 65:4, s. 899-910
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Tidskriftsartikel (refereegranskat)abstract
- Objective The presence of antibodies against cyclic citrullinated peptides has been demonstrated to precede the onset of symptoms of rheumatoid arthritis (RA) by several years. The aim of this study was to analyze antibodies against 10 citrullinated autoantigen-derived peptides for reactivity before the onset of RA symptoms. Methods A casecontrol study was conducted within the Medical Biobank of Northern Sweden. The study was performed in 409 individuals, 386 of whom donated 717 blood samples before the onset of symptoms of RA (pre-patients). The median period of time predating the onset of RA was 7.4 years. A total of 1,305 population-based control subjects were also studied. Antibodies to 10 citrullinated peptides, fibrinogen 573 (Fib573), Fib591, Fib3652, Fib72, Fib74, -enolase (citrullinated -enolase peptide 1 [CEP-1]), triple-helical type II collagen peptide C1 (citC1III), filaggrin, vimentin 217 (Vim217), and Vim6075, were analyzed using a microarray system. Results The fluorescence intensity of antibodies against Fib3652, Fib74, CEP-1, citC1III, and filaggrin was significantly increased in pre-patients compared with controls (P < 0.001). The levels of the earliest-detectable antibodies (Fib591 and Vim6075) fluctuated over time, with only a slight increase after the onset of disease. The frequency of antibodies against Fib3652, CEP-1, and filaggrin increased gradually, reaching the highest levels before symptom onset. The frequency of a cluster of antibodies, citC1III, Fib573, and Fib74, increased only slightly before the onset of symptoms but increased prominently after disease onset. The odds ratio for the development of RA in individuals expressing both CEP-1 and Fib3652 antibodies (using data from samples obtained <3.35 years predating symptom onset) was 40.4 (95% confidence interval 19.882.3) compared with having either antibody alone. Conclusion Development of an immune response toward citrullinated peptides is initially restricted but expands with time to induce a more specific response, with levels, particularly those of antibodies against CEP-1, Fib3652, and filaggrin, increasing during the predating time period closer to the onset of symptoms.
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- Brynolfsson, Johan, et al.
(författare)
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Least Squares and Maximum Likelihood Estimation of Mixed Spectra
- 2018
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Ingår i: 26th European Signal Processing Conference, EUSIPCO 2018.. - 9789082797015 ; , s. 2345-2349
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Konferensbidrag (refereegranskat)abstract
- In this paper, we propose a novel 1-D spectralestimator for signals with mixed spectra. The proposed methodis partly based on the recently introduced smooth spectralestimator LIMES, in which the smoothness is accounted for byassuming linearity within predefined segments of the spectrum.The proposed method utilizes this formulation but also allowssegments to change size to better estimate the spectrum, therebyallowing for the estimation of spectra that are neither completelysmooth or sparse in frequency, but rather contains a mixtureof such components. Using simulated data, we illustrate theperformance of the proposed estimator, comparing to other recentspectral estimation techniques.
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- Brynolfsson, Johan, et al.
(författare)
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Smooth Time-Frequency Estimation using Covariance Fitting
- 2014
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Ingår i: Acoustics, Speech and Signal Processing (ICASSP), 2014 IEEE International Conference on. - 1520-6149. ; , s. 779-783
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Konferensbidrag (refereegranskat)abstract
- In this paper, we introduce a time-frequency spectral estimator for smooth spectra, allowing for irregularly sampled measurements. A non-parametric representation of the time dependent (TD) covariance matrix is formed by assuming that the spectrum is piecewise linear. Using this representation, the time-frequency spectrum is then estimated by solving a convex covariance fitting problem, which also, as a byproduct, provides an enhanced estimation of the TD covariance matrix. Numerical examples using simulated non-stationary processes show the preferable performance of the proposed method as compared to the classical Wigner-Ville distribution and a smoothed spectrogram.
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