Inflammation-related plasma and CSF biomarkers for multiple sclerosis
| Autor: | Huang, J, Khademi, M, Fugger, L, Lindhe, Ö, Novakova, L, Axelsson, M, Malmeström, C, Constantinescu, C, Lycke, J, Piehl, F, Olsson, T, Kockum, I |
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| Rok vydání: | 2020 |
| Předmět: |
Inflammation/blood
EXPRESSION Adult Chemokine CCL11 Male Proteomics Proximity extension assay BLOOD Multiple Sclerosis multiple sclerosis PLACEBO-CONTROLLED TRIAL Severity of Illness Index cerebrospinal fluid Cohort Studies Young Adult Immunology and Inflammation CEREBROSPINAL-FLUID extension assay Humans Chemokine CCL11/analysis NATALIZUMAB Inflammation Chemokine CCL20 Multiple Sclerosis/blood DISABILITY proximity Reproducibility of Results biomarkers NEUROFILAMENT Chemokine CCL20/blood MULTIPLE-SCLEROSIS Middle Aged Biological Sciences Prognosis CHEMOKINES Case-Control Studies T-CELLS proximity extension assay Female Biomarkers/blood |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Huang, J, Khademi, M, Fugger, L, Lindhe, Ö, Novakova, L, Axelsson, M, Malmeström, C, Constantinescu, C, Lycke, J, Piehl, F, Olsson, T & Kockum, I 2020, ' Inflammation-related plasma and CSF biomarkers for multiple sclerosis ', Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 23, pp. 12952-12960 . https://doi.org/10.1073/pnas.1912839117 |
| ISSN: | 1091-6490 |
| Popis: | Significance Molecular biomarkers for multiple sclerosis have so far mainly been limited to measures in cerebrospinal fluid (CSF). Here, we identified additional biomarkers for multiple sclerosis, 2 in plasma as well as 10 in CSF. Furthermore, we identified 2 biomarkers: eotaxin-1 (CCL11), associated with disease duration and progression in both CSF and plasma, and plasma CCL20 which showed association with disease severity. However, these findings will require further validation. The capability of measuring biomarkers for multiple sclerosis may assist in the monitoring of patients during routine clinical care such as assessing treatment response but may also allow researchers to more accurately characterize pathological processes of inflammation and neurodegeneration in both the CNS and periphery of patients with multiple sclerosis. Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We have investigated a broad set of protein biomarkers in cerebrospinal fluid (CSF) and plasma using a highly sensitive proteomic immunoassay. Cases from two independent cohorts were compared with healthy controls and patients with other neurological diseases. We identified and replicated 10 cerebrospinal fluid proteins including IL-12B, CD5, MIP-1a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neurofilament light chain (area under the curve [AUC] = 0.95). Two plasma proteins, OSM and HGF, were also associated with multiple sclerosis in comparison to healthy controls. Sensitivity and specificity of combined CSF and plasma markers for multiple sclerosis were 85.7% and 73.5%, respectively. In the discovery cohort, eotaxin-1 (CCL11) was associated with disease duration particularly in patients who had secondary progressive disease (PCSF < 4 × 10−5, Pplasma < 4 × 10−5), and plasma CCL20 was associated with disease severity (P = 4 × 10−5), although both require further validation. Treatment with natalizumab and fingolimod showed different compartmental changes in protein levels of CSF and peripheral blood, respectively, including many disease-associated markers (e.g., IL12B, CD5) showing potential application for both diagnosing disease and monitoring treatment efficacy. We report a number of multiple sclerosis biomarkers in CSF and plasma for early disease detection and potential indicators for disease activity. Of particular importance is the set of markers discovered in blood, where validated biomarkers are lacking. |
| Databáze: | OpenAIRE |
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