Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis.
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Åkesson J, Hojjati S, Hellberg S, Raffetseder J, Khademi M, Rynkowski R, Kockum I, Altafini C, Lubovac-Pilav Z, Mellergård J, Jenmalm MC, Piehl F, Olsson T, Ernerudh J, Gustafsson M
Nat Commun 14 (1) 6903 [2023-10-30; online 2023-10-30]
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.
Affinity Proteomics Uppsala [Service]
NGI Uppsala (SNP&SEQ Technology Platform) [Service]
National Genomics Infrastructure [Service]
PubMed 37903821
DOI 10.1038/s41467-023-42682-9
Crossref 10.1038/s41467-023-42682-9
pmc: PMC10616092
pii: 10.1038/s41467-023-42682-9