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- Hojjati, Sara, et al.
(författare)
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Dimethyl fumarate treatment in relapsing remitting MS changes the inflammatory CSF protein profile by a prominent decrease in T-helper 1 immunity
- 2023
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Ingår i: Multiple Sclerosis and Related Disorders. - : ELSEVIER SCI LTD. - 2211-0348 .- 2211-0356. ; 80
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dimethyl fumarate (DMF) is a common treatment for multiple sclerosis (MS), but its mechanisms of action are not fully understood. Targeted proteomics offers insights into effects of DMF and biomarkers for treatment responses.Objectives: To assess influence of DMF on inflammation-and neuro-associated proteins in plasma and cerebro-spinal fluid (CSF) in MS and to reveal biomarkers for predicting treatment responses.Methods: Using the high-sensitivity and high-specificity method of proximity extension assay (PEA), we measured 182 inflammation-and neuro-associated proteins in paired plasma (n = 28) and CSF (n = 12) samples before and after one year of DMF treatment. Disease activity was evaluated through clinical examination and MRI. Statistical tests, network analysis, and regression models were used.Results: Several proteins including T-helper 1 (Th1)-associated proteins (CXCL10, CXCL11, granzyme A, IL-12p70, lymphotoxin-alpha) were consistently decreased in CSF, while IL-7 was increased after one year of treatment. The changes in plasma protein levels did not follow the same pattern as in CSF. Logistic regression models identified potential biomarker candidates (including plexins and neurotrophins) for prediction of treatment response.Conclusions: DMF treatment induced prominent changes in CSF proteins, consistently reducing Th1-associated pro-inflammatory proteins. Neurodegeneration-related CSF proteins were able to predict treatment response. Protein biomarkers hold promise for personalized medicine.
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| 3. |
- Svenvik, Maria, 1973-, et al.
(författare)
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Plasma oxylipin levels associated with preterm birth in preterm labor✰
- 2021
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Ingår i: Prostaglandins, Leukotrienes and Essential Fatty Acids. - : Elsevier. - 0952-3278 .- 1532-2823. ; 166
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Preterm labor is a common clinical problem in obstetrics. Since the majority of women with preterm labor eventually deliver at full term, biomarkers are needed to more accurately predict who will deliver preterm. Oxylipins, given their importance in inflammation regulation, are highly interesting in this respect since labor is an inflammatory process.Methods Eighty women with preterm labor before 34 weeks of gestation were enrolled in a prospective observational multi-center cohort study. Oxylipin levels of 67 analytes in plasma samples were analyzed by liquid chromatography coupled to tandem mass spectrometry.Results Twenty-one (26%) of the women delivered before 34 weeks of gestation, and of those women, fourteen delivered within 48 h of admission. Logistic multivariate regression showed that lower levels of 9,10-DiHODE were associated with delivery before 34 weeks of gestation (aOR 0.12 (0.024–0.62)) and within 48 h ((aOR 0.13 (0.019–0.93)). Furthermore, higher levels of 11,12-DiHETrE were associated with delivery before 34 weeks of gestation ((aOR 6.19 (1.17–32.7)) and higher levels of 8-HETE were associated with delivery within 48 h ((aOR 5.01 (1.13–22.14)).Conclusions The oxylipin 9,10-DiHODE may be protective in preterm labor, both for delivery after 34 weeks of gestation and for delivery later than 48 h of admission, whereas 11,12-DiHETrE and 8-HETE display the opposite effect. Larger studies are needed to validate these mediators as biomarkers for prediction of preterm birth following preterm labor.
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| 4. |
- Åkesson, Julia, et al.
(författare)
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Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Sensitive and reliable protein biomarkers are needed to predict disease trajectory and personalize treatment strategies for multiple sclerosis (MS). Here, we use the highly sensitive proximity-extension assay combined with next-generation sequencing (Olink Explore) to quantify 1463 proteins in cerebrospinal fluid (CSF) and plasma from 143 people with early-stage MS and 43 healthy controls. With longitudinally followed discovery and replication cohorts, we identify CSF proteins that consistently predicted both short- and long-term disease progression. Lower levels of neurofilament light chain (NfL) in CSF is superior in predicting the absence of disease activity two years after sampling (replication AUC = 0.77) compared to all other tested proteins. Importantly, we also identify a combination of 11 CSF proteins (CXCL13, LTA, FCN2, ICAM3, LY9, SLAMF7, TYMP, CHI3L1, FYB1, TNFRSF1B and NfL) that predict the severity of disability worsening according to the normalized age-related MS severity score (replication AUC = 0.90). The identification of these proteins may help elucidate pathogenetic processes and might aid decisions on treatment strategies for persons with MS.
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