The following article is part of conference coverage from the 8th Joint American Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) MSVirtual2020 event. Neurology Advisor‘s staff will be reporting breaking news associated with research conducted by leading experts in neurology. .
Baseline levels of the biomarker ubiquitin C-terminal hydrolase L1 (UCH-L1) measured in cerebral spinal fluid (CSF) are predictive of long-term multiple sclerosis (MS) progression, according to study results presented at the 8th Joint American Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) MSVirtual2020 event, held September 11-13, 2020.
The development of increasingly powerful MS treatments has highlighted the need for prognostic biomarkers. The investigators of this prospective cohort study sought to compare the long-term prognostic value of 4 proteins found in paired serum and CSF samples collected following MS diagnosis. Study researchers identified 67 patients who had serum collected within 5 years of their first MS symptom onset and with over 15 years of routine clinical follow-up. Using digital immunoassay, Neurofilament light Chain (NfL), Glial Fibrillary Acidic Protein (GFAP), Tau, and UCH-L1 levels were measured in serum and CSF samples from participants with MS and matched controls. Study outcomes of biomarker performance evaluated by the researchers consisted of conversion to progressive MS phenotype and achieving greater than or equal to 4 on the Expanded Disability Status Scale (EDSS).
In 3 of 4 candidate markers, baseline CSF levels were higher in participants with MS compared with controls: NfL (624 vs 277 pg/mL, respectively; P =.0001), GFAP (6900 vs 694 pg/mL, respectively; P <.0001), and Tau (15.4 vs 8.12 pg/mL, respectively; P =.0001). There was no such difference in UCH-L1 levels. In serum samples, differences between MS and control groups, although less noticeable, were found in baseline measures of NfL (10.1 vs 7.3 pg/mL, respectively; P =.0037) and GFAP (68 vs 51 pg/mL, respectively; P =.0011), but not in Tau or UCH-L1 marker levels. In receiver operating characteristic curve analyses, UCH-L1 levels in CSF samples were most predictive of developing an EDSS greater than or equal to 4 after 15 years of follow-up (AUC, 0.72; P =.003), followed by NfL levels in serum (AUC, 0.70; P=.012) and GFAP levels in CSF (AUC, 0.66; P =.03). UCH-L1 levels in CSF were also most predictive of developing a progressive MS phenotype (AUC, 0.69; P =.0097), followed by GFAP levels in CSF (AUC, 0.66; P =.024) and NfL levels in serum (AUC, 0.64; P =.057). Levels of GFAP, Tau, and UCH-L1 in serum samples, as well as Tau levels in CSF samples, were not predictive of a progressive MS phenotype nor an EDSS score of greater than or equal to 4.
Study researchers concluded that baseline CSF UCH-L1 marker levels were associated with long-term outcomes in MS and that this biomarker “was more predictive of EDSS worsening and conversion to a progressive phenotype than well-established markers NfL and GFAP.”
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Thebault S, Abdoli M, Fereshtehnejad S, Tessier D, Tabard-Cossa V, Freedman M. Comparison of serum and CSF fluid biomarkers for predicting long term disease progression in MS. Poster presented at: 8th Joint American Committee for Treatment and Research in Multiple Sclerosis and European Committee for Treatment and Research in Multiple Sclerosis MSVirtual2020 event; September 11-13, 2020; Abstract P0051.