| 1. |
- 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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| 2. |
- Bager, Jessica, et al.
(författare)
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Prevalence and early-life risk factors for tree nut sensitization and allergy in young adults
- 2021
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Ingår i: Clinical and Experimental Allergy. - : John Wiley & Sons. - 0954-7894 .- 1365-2222. ; 51:11, s. 1429-1437
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Tidskriftsartikel (refereegranskat)abstract
- Background Tree nut allergy may cause anaphylaxis. There are limited population-based studies on prevalence and early-life risk factors. Methods We evaluated the prevalence of reported symptoms and allergic sensitization to tree nuts at age 24 years in the BAMSE population-based cohort study and assessed early-life factors associated with the development of tree nut allergy. We estimated tree nut allergy prevalence, by analysing questionnaire data on tree nut ingestion and symptoms at age 12, 16 and 24 years, and IgE sensitization at age 24 years to hazelnut, walnut, pecan, cashew, pistachio, Brazil nut, almond extracts and allergen molecules Cor a 1, 9, 14 (hazelnut), Jug r 1 (walnut) and Ana o 3 (cashew). We evaluated eczema, asthma, food allergies, inherited risk of allergy and gender as potential early-life risk factors. Results Data were available for 2215/4089 (54%) BAMSE study participants, for estimation of the prevalence of tree nut sensitization (21.2%), tree nut allergy symptoms (9.8%) and combined sensitization and symptoms (7.9%, 2.1% for storage protein sensitization and symptoms, 4.3% for any sensitization and non-mild symptoms). Sixty-three per cent of sensitized individuals (295/470) were asymptomatic, but only 76/470 (16%) storage protein sensitized individuals. Egg allergy (ORadj 8.50 95% CI 2.15-33.6), eczema (ORadj 2.53 95% CI 1.21-5.32) and asthma (ORadj 5.59 95% CI 2.35-13.3)) at pre-school age were associated with future development of tree nut symptoms and storage protein sensitization. At age 24 years, tree nut allergy was associated with current eczema and with markers of current asthma severity. Sensitization to storage proteins was more strongly associated with symptoms than sensitization to whole extract for all tree nuts evaluated. Conclusions In this Swedish cohort, we found tree nut whole extract sensitization is common but usually asymptomatic. Storage protein sensitization is a more reliable indicator of tree nut symptoms. Tree nut allergy is associated with early onset, persistent and severe atopic disease.
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| 3. |
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| 4. |
- Zettergren, Anna, et al.
(författare)
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Assessing tobacco use in Swedish young adults from self-report and urinary cotinine : A validation study using the BAMSE birth cohort
- 2023
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Ingår i: BMJ Open. - 2044-6055. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Studies on health effects of tobacco often rely on self-reported exposure data, which is subjective and can lead to misclassification. The aim of this study was to describe the prevalence of cigarette smoking, snus and e-cigarette use, as well as to validate self-reported tobacco use among young adults in Sweden. Method Participants of a population-based Swedish cohort (n=3052), aged 22-25 years, assessed their tobacco use in a web questionnaire. Urinary cotinine was analysed in a subsample of the study population (n=998). The agreement between self-reported tobacco use and urinary cotinine was assessed using Cohen's Kappa coefficient (κ) at a cut-off level of 50 ng/mL. Results Patterns of tobacco use differed between men and women. Among men, 20.0% reported daily snus use, 5.8% daily cigarette smoking and 5.6% any e-cigarette use. In contrast, 3.2% of the women reported daily snus use, 9.0% daily cigarette smoking and 2.4% any e-cigarette use. Among the tobacco use categories, daily snus users had the highest levels of cotinine. Of reported non-tobacco users, 3.5% had cotinine levels above the cut-off, compared with 68.0% among both occasional cigarette smokers and snus users, 67.5% among all e-cigarette users and 94.7% and 97.8% among daily cigarette smokers and snus users, respectively. Agreement between self-reported tobacco use and urinary cotinine was classified as strong for daily use of cigarettes (κ=0.824) and snus (κ=0.861), while moderate to weak for occasional smoking (κ=0.618), occasional snus use (κ=0.573) and any e-cigarette use (κ=0.576). Conclusions We found high validity of self-reported tobacco use in our study population, particularly for daily tobacco use. Further, we found that daily snus users were exposed to high levels of cotinine. Together with previous findings, our results indicate good validity of self-reported tobacco use among young adults.
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| 5. |
- Bergstrom, Anna, et al.
(författare)
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Acetaminophen Attenuates Pulmonary Vascular Resistance and Pulmonary Arterial Pressure and Inhibits Cardiovascular Collapse in a Porcine Model of Endotoxemia
- 2023
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Ingår i: Shock. - : Shock Society. - 1073-2322 .- 1540-0514. ; 59:3, s. 442-448
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Tidskriftsartikel (refereegranskat)abstract
- Acetaminophen (paracetamol) is often used in critically ill patients with fever and pain; however, little is known about the effects of acetaminophen on cardiovascular function during systemic inflammation. Here, we investigated the effect of acetaminophen on changes in the systemic and pulmonary circulation induced by endotoxin (0.5 μg/kg/h) in anesthetized pigs. Endotoxin infusion led to a rapid increase in pulmonary artery (PA)-pressure and pulmonary vascular resistance index (PVRI). Acetaminophen delayed and attenuated this increase. Furthermore, acetaminophen reduced tachycardia and decreased stroke volume, accompanied by systemic inflammation, without affecting inflammatory parameters such as white blood cell count and TNF-α in blood. As a proof of concept, we injected a high dose of endotoxin (100 μg), which induced rapid cardiovascular collapse in pigs. Pigs treated with acetaminophen survived with no obvious hemodynamic instability during the 50 min observation period. In conclusion, acetaminophen attenuates the effects of endotoxin on pulmonary circulation in anesthetized pigs. This may play a role in severe systemic inflammation.
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| 6. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 7. |
- Lemonnier, Nathanaël, et al.
(författare)
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A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents
- 2020
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY. - 0105-4538 .- 1398-9995. ; 75:12, s. 3248-3260
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large-scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes.Methods: Integrated transcriptomic analysis was conducted in 1233 participants with a discovery phase using gene expression data (Human Transcriptome Array 2.0) from whole blood of 786 children from three European birth cohorts (MeDALL), and a replication phase using RNA Sequencing data from an independent cohort (EVA-PR, n = 447). Allergic diseases (asthma, atopic dermatitis, rhinitis) were considered as single disease or multimorbidity (at least two diseases), and compared with no disease.Results: Fifty genes were differentially expressed in allergic diseases. Thirty-two were not previously described in allergy. Eight genes were consistently overexpressed in all types of multimorbidity for asthma, dermatitis, and rhinitis (CLC, EMR4P, IL5RA, FRRS1, HRH4, SLC29A1, SIGLEC8, IL1RL1). All genes were replicated the in EVA-PR cohort. RT-qPCR validated the overexpression of selected genes. In MeDALL, 27 genes were differentially expressed in rhinitis alone, but none was significant for asthma or dermatitis alone. The multimorbidity signature was enriched in eosinophil-associated immune response and signal transduction. Protein-protein interaction network analysis identified IL5/JAK/STAT and IL33/ST2/IRAK/TRAF as key signaling pathways in multimorbid diseases. Synergistic effect of multimorbidity on gene expression levels was found.Conclusion: A signature of eight genes identifies multimorbidity for asthma, rhinitis, and dermatitis. Our results have clinical and mechanistic implications, and suggest that multimorbidity should be considered differently than allergic diseases occurring alone.
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| 8. |
- Nordenskjöld, Anna, 1977-, et al.
(författare)
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Randomized evaluation of beta blocker and ACE-inhibitor/angiotensin receptor blocker treatment in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA-BAT): Rationale and design
- 2021
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 231, s. 96-104
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Tidskriftsartikel (refereegranskat)abstract
- Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is common and occurs in 6-8% of all patients fulfilling the diagnostic criteria for acute myocardial infarction (AMI). This paper describes the rationale behind the trial 'Randomized Evaluation of Beta Blocker and ACE-Inhibitor/Angiotensin Receptor Blocker Treatment (ACEI/ARB) of MINOCA patients' (MINOCA-BAT) and the need to improve the secondary preventive treatment of MINOCA patients. Methods MINOCA-BAT is a registry-based, randomized, parallel, open-label, multicenter trial with 2:2 factorial design. The primary aim is to determine whether oral beta blockade compared with no oral beta blockade, and ACEI/ARB compared with no ACEI/ARB, reduce the composite endpoint of death of any cause, readmission because of AMI, ischemic stroke or heart failure in patients discharged after MINOCA without clinical signs of heart failure and with left ventricular ejection fraction >= 40%. A total of 3500 patients will be randomized into four groups; e.g. ACEI/ARB and beta blocker, beta blocker only, ACEI/ARB only and neither ACEI/ARB nor beta blocker, and followed for a mean of 4 years. Summary While patients with MINOCA have an increased risk of serious cardiovascular events and death, whether conventional secondary preventive therapies are beneficial has not been assessed in randomized trials. There is a limited basis for guideline recommendations in MINOCA. Furthermore, studies of routine clinical practice suggest that use of secondary prevention therapies in MINOCA varies considerably. Thus results from this trial may influence future treatment strategies and guidelines specific to MINOCA patients.
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