Biomarkers and Disease Activity in Multiple Sclerosis : A cohort study on patients with clinically isolated syndrome and relapsing remitting multiple sclerosis

Håkansson, Irene

doi:10.3384/diss.diva-160762

Cited by 3 publications

(5 citation statements)

References 142 publications

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“…NfL level in CSF is an established marker of ongoing neuroaxonal damage in MS, with emerging data supporting its usefulness also in the blood compartment. Furthermore, levels of NfL in both CSF and plasma/serum are also shown to decrease with disease modifying treatments [49][50][51] and CSF-NfL is able to predict short-term disease activity manifested by contrast-enhancing lesions, relapses, or both 27,45,46,[52][53][54] . Despite covering 1463 proteins in our present study, CSF-NfL stood out as the major biomarker for prediction of short-term disease activity.…”

Section: Discussionmentioning

confidence: 99%

“…Using the same NPX threshold in the replication cohort resulted in an accuracy of 0.62. To translate NPX to pg/ml, we used a fraction of our data (n = 38) from which the NfL levels were known based on previous measurement by Simoa [27][28][29] . The NPX and pg/ml measurements were highly correlated (Spearman's Correlation Coefficient (SCC) = 0.97), and the NPX threshold of 1.14 corresponded to 737 pg/ml (see "Methods").…”

Section: Nfl Is Superior In Predicting Disease Activity Over 2 Yearsmentioning

confidence: 99%

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Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis

Åkesson,

Hojjati,

Hellberg

et al. 2023

Nat Commun

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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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Section: Discussionmentioning

confidence: 99%

Section: Nfl Is Superior In Predicting Disease Activity Over 2 Yearsmentioning

confidence: 99%

Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis

Åkesson,

Hojjati,

Hellberg

et al. 2023

Nat Commun

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“…NfL is a marker of neuroaxonal damage and is already being used in MS as a CSF biomarker for disease activity. Furthermore, levels of NfL in both CSF and plasma/serum are also shown to decrease with disease modifying treatments [43][44][45] and CSF-NfL is able to predict short-term disease activity 26,46,47 . Despite covering 1463 proteins in our present study, CSF-NfL stood out as the major biomarker for prediction of short-term disease activity.…”

Section: Discussionmentioning

confidence: 99%

“…Using the same NPX threshold in the replication cohort resulted in an accuracy of 0.62. To translate NPX to pg/ml, we used a fraction of our data (n = 38) from which the NfL levels were known based on previous measurement by Simoa [26][27][28] . The NPX and pg/ml measurements were highly correlated (Spearman's Correlation Coefficient (SCC) = 0.97), and the NPX threshold of 1.14 corresponded to 737 pg/ml (see Methods).…”

Section: Nfl Is Superior In Predicting Disease Activity Over Two Yearsmentioning

confidence: 99%

Proteomics profiling reveals biomarkers for predicting diagnosis, disease activity and long-term disability outcome in multiple sclerosis

Åkesson

Hojjati

Hellberg

et al. 2023

Preprint

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To personalize multiple sclerosis (MS) treatment strategies, sensitive and reliable protein biomarkers are needed to predict disease trajectory. We used protein profiling based on the highly sensitive proximity extension assay combined with next generation sequencing (Olink Explore) to measure 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 identified CSF proteins that consistently predicted both short- and long-term disease progression. Neurofilament light chain (NfL) in CSF was confirmed as superior for predicting the absence of disease activity 2 years after sampling (replication AUC = 0.77). Importantly, we also identified a combination of 11 CSF proteins (CXCL13, LTA, FCN2, ICAM3, LY9, SLAMF7, TYMP, CHI3L1, FYB1, TNFRSF1B, NfL) that could predict the severity of disability worsening according to the normalized age-related MS severity score (replication AUC = 0.90). Identified proteins elucidate pathogenetic processes and can aid decisions of treatment strategies for people with MS.

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“…Markers such as neurofilaments light chain, neurofilaments heavy chain, glial fibrillary acidic protein, chitinase-3-like-1 (CHI3L1), cytokines (e.g., CXCL1, CXCL8, CXCL10, CXCL13, CCL22, and HMGB1), and osteopontin have been tested as biomarkers of disease activity, but no sufficient evidence exists for their reliability. [24][25][26][27][28] For the MMP-9, patients with MS had higher serum and cerebrospinal fluid (CSF) levels of MMP-9 compared with their counterparts from the general population. [29][30][31][32] The levels during relapses were significantly higher than in-between relapses making it a potential marker of current disease activity.…”

Section: Discussionmentioning

confidence: 99%

Serum Matrix Metalloproteinase-9 Level and Previous Disease Activity in Relapsing-Remitting Multiple Sclerosis

Hamdy,

Ramdan,

Mekky

et al. 2023

Int Clin Neurosci J

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Background: Matrix metalloproteinase-9 (MMP-9) is a marker of blood-brain barrier destruction, that is elevated during clinical relapses in multiple sclerosis (MS). In between relapses, MMP-9 levels decline but remain higher than the normal population. This study aimed to investigate the relation between serum MMP-9 level and disease activity in MS during relapse-free periods. Methods: This was a retrospective study conducted on adult patients with relapsing-remitting MS (RRMS) whose last relapse was≥1 month ago. Serum MMP-9 was withdrawn at the time of recruitment and correlated with parameters of disease activity. Results: Of the 40 patients recruited, 75% were women. The mean age was 36.2±8.4 years, and the mean disease duration was 7 years. Patients’ median Expanded Disability Status Scale (EDSS) was 3.5 (IQR: 2.5-5.25), the median duration since the last relapse was 3 months, and the median duration since last corticosteroid administration was 6 months. On multivariate regression analysis, there was a significant association between serum MMP-9 levels and duration since the last relapse (B: -0.004, 95% CI: -0.007- -0.002, P=0.001) as well as duration since the last corticosteroid intake (B: -0.003, 95% CI: -0.006- -0.001, P=0.005). Conclusion: Serum MMP-9 levels correlated with the duration since last relapse and duration since last corticosteroids administration during relapse-free periods.

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Biomarkers and Disease Activity in Multiple Sclerosis : A cohort study on patients with clinically isolated syndrome and relapsing remitting multiple sclerosis

Cited by 3 publications

References 142 publications

Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis

Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis

Proteomics profiling reveals biomarkers for predicting diagnosis, disease activity and long-term disability outcome in multiple sclerosis

Serum Matrix Metalloproteinase-9 Level and Previous Disease Activity in Relapsing-Remitting Multiple Sclerosis

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