| 1. |
- Saevarsdottir, S., et al.
(författare)
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Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.
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| 2. |
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| 3. |
- Lonnblom, E, et al.
(författare)
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AUTOANTIBODIES TO JOINT PROTEINS AS NOVEL BIOMARKERS FOR THE DIAGNOSIS OF UNTREATED EARLY RHEUMATOID ARTHRITIS
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 546-546
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Autoantibodies to citrullinated protein (ACPA; measured as anti-CCP; aCCP) and rheumatoid factor (RF) appear years before clinical onset of RA and are essential tools in today’s classification criteria for RA. In animal models, antibodies to joint specific proteins (JP) can induce arthritis, and they are also present at onset of RA [1]. As there is a need for increased precision for early diagnosis of RA as well as identification of different subtypes of the disease, we aim to assess whether autoantibodies to native or modified JP can be used for early and precise diagnosis of RA.ObjectivesTo study whether antibodies to JP, alone or in combination with ACPA/RF, could increase the diagnostic sensitivity and specificity in untreated early (ue)RA patients.MethodsAntibodies to JP were analysed in serum from patients in three independent ueRA cohorts as well as from population controls without rheumatic diseases (WINGA, Gothenburg and MFM-ÅUS, Malmö n=1062). ERAp (n=66), the smallest and most recent cohort was chosen for screening, and BARFOT and TIRA-2 (n=1939) for validation. We have developed a bead-based multianalyte flow immunoassay [2] and screened approx. 350 peptides derived from JPs of interest. We included monoclonal antibodies as assay calibrators and determined limit of detection (LoD). To assess positivity for autoantibodies to JP of interest above LoD, we used 5MAD (median absolute deviation) of the control populations as the cut-off.ResultsIn the ERAp cohort, 5 autoantibodies discriminated RA patients from controls with 81% sensitivity and 100% specificity (Table 1). The same autoantibodies had 68% sensitivity and 98% specificity in the combined BARFOT and TIRA-2 cohorts. Together with RF and aCCP, only 2 of the 5 autoantibodies added statistically significant diagnostic value, increasing the sensitivity from 48% to 61% with 99% specificity. In aCCP- and RF-negative ueRA patients (n=536), the novel biomarkers identified 22.5% of the patients with 99% specificity compared to controls.Table 1.Diagnostic capacity of the joint-specific antibodiesTest panelPerformanceGroup of patientsaCCP+RF+JP+SensitivitySpecificityAUC(ROC)ERApAll patients (n=66)--X81%100%89%RF and aCCP-neg patients (n=7)1------BARFOT and TIRA-2, combined dataAll patients (N=1939)--X68%98%86%All patients (N=1939)X--58%99%78%All patients (N=1939)2XX-48%100%84%All patients (N=1939)2, 3XXX61%99%86%RF and/or aCCP-pos patients (N=1403)--X84%99%93%RF and aCCP-neg patients (N=536)--X22%99%67%RA, literature valuesAnti-CCP testXN/AN/A53–71%95–96%N/A1Not analysed due to lack of power2This patient population is both aCCP+ and RF+3Only 2 of the 5 autoantibodies added statistically significant to the diagnostic valueAUC, Area under the curve; ROC, receiver operating characteristic curve; N/A, not applicable. Controls without rheumatic diseases: N=935 for BARFOT / TIRA-2 and N=27 for ERAp.ConclusionAutoantibodies to JP discriminate ueRA patients better then aCCP and RF alone and add an increased diagnostic value in particular for seronegative patients.References[1]Holmdahl, R., V. Malmstrom, and H. Burkhardt, Autoimmune priming, tissue attack and chronic inflammation - the three stages of rheumatoid arthritis. Eur J Immunol, 2014. 44(6): p. 1593-9.[2]Viljanen, J., et al., Synthesis of an Array of Triple-Helical Peptides from Type II Collagen for Multiplex Analysis of Autoantibodies in Rheumatoid Arthritis. ACS Chem Biol, 2020. 15(9): p. 2605-2615. Correction: ACS Chem Biol, 2020. 15(11): p. 3072AcknowledgementsBARFOT study group.Disclosure of InterestsErik Lönnblom: None declared, Monica Leu Agelii: None declared, Outi Sareila Employee of: Part time employee in Vacara AB, Ingiäld Hafström: None declared, Maria Andersson: None declared, Lei Cheng: None declared, Göran Bergström: None declared, Anna-Karin H Ekwall: None declared, Anna Rudin: None declared, Alf Kastbom: None declared, Christopher Sjowall: None declared, Bingze Xu: None declared, Lennart T.H. Jacobsson: None declared, Johan Viljanen: None declared, Jan Kihlberg: None declared, Inger Gjertsson: None declared, Rikard Holmdahl Shareholder of: Rikard Holmdahl the founder of Vacara AB.
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| 4. |
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| 5. |
- Nilsson, Jenny, et al.
(författare)
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Influence of Age and Sex on Disease Course and Treatment in Rheumatoid Arthritis
- 2021
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Ingår i: Open Access Rheumatology-Research and Reviews. - 1179-156X. ; 13, s. 123-138
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Tidskriftsartikel (refereegranskat)abstract
- Objective: More than 50% of patients with rheumatoid arthritis (RA) are >65 years at diagnosis. Age of onset and sex may influence the disease course, outcome and treatment. This study follows a large cohort of patients with early RA to assess contributions of age and sex to disease outcomes. Methods: Patients from the BARFOT cohort, n=2837 (68% women), were followed for eight years at predefined time points to assess inflammation, function, joint destruction and treatment with disease modifying anti-rheumatic drugs (DMARDs) and glucocorticoids (GC). The patients were divided by sex and age at inclusion (<40, 40-54, 55-69 and >= 70 years). Results: For both sexes, disease activity, function and pain improved over time, significantly more in men than in women in all age groups. In men, those <40 years displayed significantly lower DAS28 compared with all other groups. This group was also the least represented group in the study. The Sharp van der Heijde Score (SHS) increased over time in both sexes and all age groups. Women >= 70 years showed less improvement in disability and the highest progression of SHS mainly due to increased joint space narrowing. Patients <40 years were more likely to receive biological DMARDs, while those >= 70 years more often received only GC treatment. Conclusion: There were significant age- and sex-dependent differences in the medical treatment and in outcome of RA 8 years after diagnosis. The differences were most pronounced in men<40 and women >= 70 years, but whether they are due to disease phenotype or treatment is unclear.
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| 6. |
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| 7. |
- 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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| 8. |
- Andersson, Maria L.E., et al.
(författare)
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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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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:7, s. 1110-1119
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Tidskriftsartikel (refereegranskat)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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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Blomqvist, L., et al.
(författare)
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Limited evidence for the use of imaging to detect prostate cancer : a systematic review
- 2014
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Ingår i: European Journal of Radiology. - : Elsevier. - 0720-048X .- 1872-7727. ; 83:9, s. 1601-1606
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Forskningsöversikt (refereegranskat)abstract
- Objective: To assess the diagnostic accuracy of imaging technologies for detecting prostate cancer in patients with elevated PSA-values or suspected findings on clinical examination.Methods: The databases Medline, EMBASE, Cochrane, CRD HTA/DARE/NHS EED and EconLit were searched until June 2013. Pre-determined inclusion criteria were used to select full text articles. Risk of bias in individual studies was rated according to QUADAS or AMSTAR. Abstracts and full text articles were assessed independently by two reviewers. The performance of diagnostic imaging was compared with systematic biopsies (reference standard) and sensitivity and specificity were calculated.Results: The literature search yielded 5141 abstracts, which were reviewed by two independent reviewers. Of these 4852 were excluded since they did not meet the inclusion criteria. 288 articles were reviewed in full text for quality assessment. Six studies, three using MRI and three using transrectal ultrasound were included. All were rated as high risk of bias. Relevant studies on PET/CT were not identified.Conclusion: Despite clinical use, there is insufficient evidence regarding the accuracy of imaging technologies for detecting cancer in patients with suspected prostate cancer using TRUS guided systematic biopsies as reference standard. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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| 13. |
- Grimsholm, Ola, 1979, et al.
(författare)
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Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding V(H)81X-expressing B cells
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Random recombination of antibody heavy- and light-chain genes results in a diverse B-cell receptor (BCR) repertoire including self-reactive BCRs. However, tolerance mechanisms that prevent the development of self-reactive B cells remain incompletely understood. The absence of the surrogate light chain, which assembles with antibody heavy chain forming a pre-BCR, leads to production of antinuclear antibodies (ANAs). Here we show that the naive follicular B-cell pool is enriched for cells expressing prototypic ANA heavy chains in these mice in a non-autoimmune background with a broad antibody repertoire. This results in the spontaneous formation of T-cell-dependent germinal centres that are enriched with B cells expressing prototypic ANA heavy chains. However, peripheral tolerance appears maintained by selection thresholds on cells entering the memory B-cell and plasma cell pools, as exemplified by the exclusion of cells expressing the intrinsically self-reactive V(H)81X from both pools.
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| 14. |
- He, Yibo, et al.
(författare)
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A subset of antibodies targeting citrullinated proteins confers protection from rheumatoid arthritis.
- 2023
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Although elevated levels of anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA), the in vivo functions of these antibodies remain unclear. Here, we have expressed monoclonal ACPAs derived from patients with RA, and analyzed their functions in mice, as well as their specificities. None of the ACPAs showed arthritogenicity nor induced pain-associated behavior in mice. However, one of the antibodies, clone E4, protected mice from antibody-induced arthritis. E4 showed a binding pattern restricted to skin, macrophages and dendritic cells in lymphoid tissue, and cartilage derived from mouse and human arthritic joints. Proteomic analysis confirmed that E4 strongly binds to macrophages and certainRA synovial fluid proteins such as α-enolase. The protective effect of E4 was epitope-specific and dependent on the interaction between E4-citrullinated α-enolase immune complexes with FCGR2B on macrophages, resulting in increased IL-10 secretion and reduced osteoclastogenesis. These findings suggest that a subset of ACPAs have therapeutic potential in RA.
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| 15. |
- Henningsson, Louise, 1979, et al.
(författare)
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Interleukin 15 Mediates Joint Destruction in Staphylococcus Aureus Arthritis
- 2012
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 206:5, s. 687-696
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Tidskriftsartikel (refereegranskat)abstract
- Background. Staphylococcus aureus arthritis causes severe and rapid joint damage despite antibiotics. Thus, there is a need to identify new treatment targets in addition to antibiotics. Lately, interleukin 15 (IL-15) has been implicated both in osteoclastogenesis and in bacterial clearance-2 important issues in S. aureus-induced joint destruction. This has prompted us to investigate the importance of IL-15 in S. aureus-induced arthritis. Methods.Toxic shock syndrome toxin-1 producing S. aureus was intravenously inoculated in IL-15 knockout and wildtype mice and in wildtype mice treated with anti-IL-15 antibodies (aIL-15ab) or isotype control antibody. Results.Absence of IL-15, either in knockout mice or after treatment with aIL-15ab, significantly reduced weight loss compared with controls during the infection. The severity of synovitis and joint destruction was significantly decreased in IL-15 knockout and aIL-15ab treated mice compared with controls. In IL-15 knockout mice there was a reduced number of osteoclasts in the joints. The host's ability to clear bacteria was not influenced in the IL-15 knockout mice, but significantly increased after treatment with aIL-15ab. Conclusions.IL-15 is a mediator of joint destruction in S. aureus-induced arthritis and contributes to general morbidity, which makes this cytokine an interesting treatment target in addition to conventional antibiotics.
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| 16. |
- Kharlamova, N., et al.
(författare)
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False Positive Results in SARS-CoV-2 Serological Tests for Samples From Patients With Chronic Inflammatory Diseases
- 2021
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic inflammatory diseases are often treated with immunosuppressants and therefore are of particular concern during the SARS-CoV-2 pandemic. Serological tests will improve our understanding of the infection and immunity in this population, unless they tests give false positive results. The aim of this study was to evaluate the specificity of SARS-Cov-2 serological assays using samples from patients with chronic inflammatory diseases collected prior to April 2019, thus defined as negative. Samples from patients with multiple sclerosis (MS, n=10), rheumatoid arthritis (RA, n=47) with or without rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (anti-CCP2) and systemic lupus erythematosus (SLE, n=10) with or without RF, were analyzed for SARS-CoV-2 antibodies using 17 commercially available lateral flow assays (LFA), two ELISA kits and one in-house developed IgG multiplex bead-based assay. Six LFA and the in-house validated IgG assay correctly produced negative results for all samples. However, the majority of assays (n=13), gave false positive signal for samples from patients with RA and SLE. This was most notable in samples from RF positive RA patients. No false positive samples were detected in any assay using samples from patients with MS. Poor specificity of commercial serological assays could possibly be, at least partly, due to interfering antibodies in samples from patients with chronic inflammatory diseases. For these patients, the risk of false positivity should be considered when interpreting results of the SARS-CoV-2 serological assays.
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| 17. |
- Landgren, Anton J., 1989, et al.
(författare)
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Serum IL-23 significantly decreased in obese patients with psoriatic arthritis six months after a structured weight loss intervention.
- 2023
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Ingår i: Arthritis research & therapy. - 1478-6362. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Patients with psoriatic arthritis (PsA) are frequently obese. We have previously shown decreased disease activity in patients with PsA with a body mass index (BMI)≥33kg/m2 following weight loss treatment with Very Low Energy Diet (VLED), resulting in a median weight loss of 18.6% at six months (M6) after baseline (BL). In this study we assessed the effects of VLED on cytokines and adipokines at M6 in the same patients with PsA and controls (matched on sex, age and weight).VLED (640kcal/day) during 12 or 16weeks, depending on BL BMI<40 or≥40kg/m2, was taken and followed by an energy-restricted diet. Cytokines and adipokines were measured with Magnetic Luminex Assays at BL and M6.Serum interleukin (IL)-23, (median (interquartile range) 0.40 (0.17-0.54) ng/mL vs. 0.18 (0.10-0.30) ng/mL, p<0.001) and leptin (26.28 (14.35-48.73) ng/mL vs. 9.25 (4.40-16.24) ng/mL, p<0.001) was significantly decreased in patients with PsA. Serum total (tot)-adiponectin and high molecular weight (HMW) adiponectin increased significantly. Similar findings were found in controls. Also, in patients with PsA, ∆BMI was positively correlated with ∆IL-23 (rS=0.671, p<0.001). In addition, significant positive correlations were found between ΔBMI and ΔDisease Activity Score (DAS28CRP), ΔCRP, Δtumor necrosis factor (TNF)-α, ΔIL-13, ∆IL-17 and Δleptin, and negative correlations between ΔBMI and Δtot-adiponectin.Weight loss was associated with decreased levels of leptin and cytokines, in particular IL-23. These findings may partly explain the anti-inflammatory effect of weight reduction in PsA.ClinicalTrials.gov identifier: NCT02917434, registered on September 21, 2016, retrospectively registered.
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| 18. |
- Leu Agelii, Monica, 1977, et al.
(författare)
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Disease activity trajectories in rheumatoid arthritis: a tool for prediction of outcome
- 2021
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 501:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Objective Predicting treatment response and disease progression in rheumatoid arthritis (RA) remains an elusive endeavour. Identifying subgroups of patients with similar progression is essential for understanding what hinders improvement. However, this cannot be achieved with response criteria based on current versus previous Disease Activity Scores, as they lack the time component. We propose a longitudinal approach that identifies subgroups of patients while capturing their evolution across several clinical outcomes simultaneously (multi-trajectories). Method For exploration, the RA cohort BARFOT (n = 2829) was used to identify 24 month post-diagnosis simultaneous trajectories of 28-joint Disease Activity Score and its components. Measurements were available at inclusion (0), 3, 6, 12, 24, and 60 months. Multi-trajectories were found with latent class growth modelling. For validation, the TIRA-2 cohort (n = 504) was used. Radiographic changes, assessed by the modified Sharp van der Heijde score, were correlated with trajectory membership. Results Three multi-trajectories were identified, with 39.6% of the patients in the lowest and 18.9% in the highest (worst) trajectory. Patients in the worst trajectory had on average eight tender and six swollen joints after 24 months. Radiographic changes at 24 and 60 months were significantly increased from the lowest to the highest trajectory. Conclusion Multi-trajectories constitute a powerful tool for identifying subgroups of RA patients and could be used in future studies searching for predictive biomarkers for disease progression. The evolution and shape of the trajectories in TIRA-2 were very similar to those in BARFOT, even though TIRA-2 is a newer cohort.
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| 19. |
- 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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| 20. |
- Polte, Christian Lars, et al.
(författare)
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Cardiac Positron Emission Tomography: a Clinical Perspective
- 2016
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Ingår i: Current Cardiovascular Imaging Reports. - : Springer Science and Business Media LLC. - 1941-9066 .- 1941-9074. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- © 2016, Springer Science+Business Media New York. Cardiac positron emission tomography is a powerful, quantitative, non-invasive imaging modality, which adds valuable diagnostic and prognostic information to the clinical work-up. Myocardial perfusion and viability imaging are, as a result of continuously growing evidence, established clinical indications that may be cost-effective, due to the high diagnostic accuracy of cardiac positron emission tomography, despite high single-test costs. In the field of inflammation imaging, new indications are entering the clinical arena, which may contribute to a better diagnosis and overall patient care, as for instance in patients with cardiac sarcoidosis, prosthetic valve endocarditis and cardiac device infections. This review will discuss the individual strengths and weaknesses of cardiac positron emission tomography and, hence, the resulting clinical usefulness based on the current evidence for an individualized, patient-centered imaging approach.
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| 21. |
- Svensson, Björn, et al.
(författare)
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Erosion-free rheumatoid arthritis: clinical and conceptional implications-a BARFOT study
- 2022
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Ingår i: Bmc Rheumatology. - : Springer Science and Business Media LLC. - 2520-1026. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBone erosions may appear early or later during rheumatoid arthritis (RA), causing joint damage and functional impairment. However, in some patients erosions do not occur, even after several years of disease. This study evaluates the prevalence, clinical relevance and possible predictors of erosion-free RA. MethodsSix hundred and eight patients from an early RA cohort (BARFOT) having radiographs of hands and feet at inclusion and after 1, 2, 5 and 8 years were studied. Clinical and functional assessments were performed on all these time-points. ResultsIn all, 144 patients (24%) did not develop erosions up to 8 years follow-up (Never erosive group), while 464 patients (76%) had erosions on one or more assessments (Ever erosive group). At diagnosis, the patients in the Never erosive group were significantly younger, satisfied fewer ACR criteria, and were less frequently RF- and/or anti-CCP- positive compared with those in the Ever erosive group. The Never erosive patients had consistently more tender joints, lower erythrocyte sedimentation rate (ESR) and, from two years and onwards, fewer swollen joints. Absence of rheumatoid factor (RF) and/or anti-CCP were strong independent predictors for erosion-free disease. The erosion-free patients were less frequently treated with DMARDs and/or prednisolone. ConclusionsOne-quarter of the patients was erosion-free during eight years in this early RA cohort. Erosion-free patients had a less severe disease course as to disease activity and were more often seronegative compared with those with erosive disease. The results suggest that non-erosive RA represents a milder form of RA.
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| 22. |
- Ulmert, David, et al.
(författare)
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A novel automated platform for quantifying the extent of skeletal tumour involvement in prostate cancer patients using the bone scan index
- 2012
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 62:1, s. 78-84
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is little consensus on a standard approach to analysing bone scan images. The Bone Scan Index (BSI) is predictive of survival in patients with progressive prostate cancer (PCa), but the popularity of this metric is hampered by the tedium of the manual calculation. Objective: Develop a fully automated method of quantifying the BSI and determining the clinical value of automated BSI measurements beyond conventional clinical and pathologic features. Design, setting, and participants: We conditioned a computer-assisted diagnosis system identifying metastatic lesions on a bone scan to automatically compute BSI measurements. A training group of 795 bone scans was used in the conditioning process. Independent validation of the method used bone scans obtained ≤3 mo from diagnosis of 384 PCa cases in two large population-based cohorts. An experienced analyser (blinded to case identity, prior BSI, and outcome) scored the BSI measurements twice. We measured prediction of outcome using pretreatment Gleason score, clinical stage, and prostate-specific antigen with models that also incorporated either manual or automated BSI measurements. Measurements: The agreement between methods was evaluated using Pearson's correlation coefficient. Discrimination between prognostic models was assessed using the concordance index (C-index). Results and limitations: Manual and automated BSI measurements were strongly correlated (ρ = 0.80), correlated more closely (ρ = 0.93) when excluding cases with BSI scores ≥10 (1.8%), and were independently associated with PCa death (p < 0.0001 for each) when added to the prediction model. Predictive accuracy of the base model (C-index: 0.768; 95% confidence interval [CI], 0.702-0.837) increased to 0.794 (95% CI, 0.727-0.860) by adding manual BSI scoring, and increased to 0.825 (95% CI, 0.754-0.881) by adding automated BSI scoring to the base model. Conclusions: Automated BSI scoring, with its 100% reproducibility, reduces turnaround time, eliminates operator-dependent subjectivity, and provides important clinical information comparable to that of manual BSI scoring. © 2012 European Association of Urology.
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- Vermeij, L. A., et al.
(författare)
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Disease-regulated local IL-10 gene therapy diminishes synovitis and cartilage proteoglycan depletion in experimental arthritis
- 2015
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 74:11, s. 2084-2091
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Rheumatoid arthritis is a chronic destructive autoimmune disease, but the course is unpredictable in individual patients. An attractive treatment would provide a disease-regulated therapy that offers personalised drug delivery. Therefore, we expressed the anti-inflammatory interleukin-10 (IL-10) gene under the control of inflammation-dependent promoters in a mouse model of arthritis. Methods Proximal promoters of S100a8, Cxcl1, Mmp13, Saa3, IL-1b and Tsg6 were selected by whole-genome expression analysis of inflamed synovial tissues from arthritic mice. Mice were injected intraarticularly in knee joints with lentiviral vectors expressing a luciferase reporter or the therapeutic protein IL-10 under control of the Saa3 or Mmp13 promoter. After 4 days, arthritis was induced by intraarticular injection of streptococcal cell walls (SCW). At different time points after arthritis induction, in vivo bioluminescent imaging was performed and knee joints were dissected for histological and RNA analysis. Results The disease-regulated promoter-luciferase reporter constructs showed different activation profiles during the course of the disease. The Saa3 and Mmp13 promoters were significantly induced at day 1 or day 4 after arthritis induction respectively and selected for further research. Overexpression of IL-10 using these two disease-inducible promoters resulted in less synovitis and markedly diminished cartilage proteoglycan depletion and in upregulation of IL-1Ra and SOCS3 gene expression. Conclusions Our study shows that promoters of genes that are expressed locally during arthritis can be candidates for disease-regulated overexpression of biologics into arthritic joints, as shown for IL-10 in SCW arthritis. The disease-inducible approach might be promising for future tailor-made local gene therapy in arthritis.
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