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2023 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 14, no 1Article in journal (Refereed) Published
Abstract [en]
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.
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-199196 (URN)10.1038/s41467-023-42682-9 (DOI)
Note
Funding: The study was funded by the Swedish Foundation for Strategic Research (SB16-0011 [M.G., J.E.]), the Swedish Brain Foundation, Knut and Alice Wallenberg Foundation, and Margareth AF Ugglas Foundation, Swedish Research Council (2019-04193 [M.G.], 2018-02776 [J.E.], 2020-02700 [F.P.], 2020-00014 [Z.L.P.], 2021-03092 [J.E.]), the Medical Research Council of Southeast Sweden (FORSS-315121 [J.E.]), NEURO Sweden (F2018-0052 [J.E.]), ALF grants, Region Östergötland, the Swedish Foundation for MS Research and the European Union’s Marie Sklodowska-Curie (813863 [J.E.]). The authors would like to acknowledge support of the Clinical biomarker facility at SciLifeLab Sweden for providing assistance in protein analyses.
2023-11-162023-11-162023-11-16Bibliographically approved