L Novakova1, M Axelsson2, C Malmeström2, H Zetterberg3, K Blennow4, A Svenningsson5, J Lycke2. 1. Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg, Sweden. Electronic address: lenka.novakova@vgregion.se. 2. Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg, Sweden. 3. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; UK Dementia Research Institute at UCL, London, UK. 4. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 5. Department of Clinical Sciences Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
Abstract
BACKGROUND: Cerebrospinal fluid (CSF) levels of neurofilament light (NFL), a biomarker of axonal damage, and CXCL13, a chemokine involved in B-cell regulation, are both associated with disease activity in multiple sclerosis (MS). OBJECTIVE: To explore the potential of NFL and CXCL13 to detect residual disease activity in patients with no signs of clinical or ongoing radiological activity and to study the clinical relevance of such activity. METHODS: NFL and CXCL13 concentrations were determined with ELISA in CSF obtained from 90 relapsing-remitting (RR) MS and 47 Progressive (Pr) MS (including primary and secondary PrMS) at baseline and after 12 months of follow-up. The patients were assessed at baseline, before initiating or switching disease modifying therapy (DMT) and again after 12 and 27 months of follow-up. RESULTS: All patients with ongoing disease activity (relapse or contrast-enhancing lesions on MRI) had increased NFL or CXCL13. The proportion of RRMS and PrMS patients without ongoing disease activity with elevation of either NFL or CXCL13 (residual disease activity) was 39% and 50%, respectively, and both were increased in 11% and 16%, respectively. The treatment with DMTs decreased the proportion with residual disease activity in both RRMS and PrMS significantly. We could not show any significant association between residual disease activity and clinical or MRI measures at 12 or 27 months of follow-up. CONCLUSIONS: Although most of this real-world study population had been treated with second-line DMTs and achieved clinical and radiological stability, a significant proportion of patients still displayed increased CSF levels of both NFL and CXCL13, indicating residual disease activity. Thus, these markers seemed considerably more sensitive to disease activity than clinical and MRI measures. However, the long-term clinical significance of such activity remains to be determined.
BACKGROUND: Cerebrospinal fluid (CSF) levels of neurofilament light (NFL), a biomarker of axonal damage, and CXCL13, a chemokine involved in B-cell regulation, are both associated with disease activity in multiple sclerosis (MS). OBJECTIVE: To explore the potential of NFL and CXCL13 to detect residual disease activity in patients with no signs of clinical or ongoing radiological activity and to study the clinical relevance of such activity. METHODS: NFL and CXCL13 concentrations were determined with ELISA in CSF obtained from 90 relapsing-remitting (RR) MS and 47 Progressive (Pr) MS (including primary and secondary PrMS) at baseline and after 12 months of follow-up. The patients were assessed at baseline, before initiating or switching disease modifying therapy (DMT) and again after 12 and 27 months of follow-up. RESULTS: All patients with ongoing disease activity (relapse or contrast-enhancing lesions on MRI) had increased NFL or CXCL13. The proportion of RRMS and PrMS patients without ongoing disease activity with elevation of either NFL or CXCL13 (residual disease activity) was 39% and 50%, respectively, and both were increased in 11% and 16%, respectively. The treatment with DMTs decreased the proportion with residual disease activity in both RRMS and PrMS significantly. We could not show any significant association between residual disease activity and clinical or MRI measures at 12 or 27 months of follow-up. CONCLUSIONS: Although most of this real-world study population had been treated with second-line DMTs and achieved clinical and radiological stability, a significant proportion of patients still displayed increased CSF levels of both NFL and CXCL13, indicating residual disease activity. Thus, these markers seemed considerably more sensitive to disease activity than clinical and MRI measures. However, the long-term clinical significance of such activity remains to be determined.
Authors: Igal Rosenstein; Markus Axelsson; Lenka Novakova; Kaj Blennow; Henrik Zetterberg; Jan Lycke Journal: Mult Scler Date: 2021-08-16 Impact factor: 5.855
Authors: Magnus Johnsson; Helen H Farman; Kaj Blennow; Henrik Zetterberg; Clas Malmeström; Markus Axelsson; Jan Lycke Journal: Mult Scler Date: 2022-07-20 Impact factor: 5.855
Authors: Tamás Biernacki; Zsófia Kokas; Dániel Sandi; Judit Füvesi; Zsanett Fricska-Nagy; Péter Faragó; Tamás Zsigmond Kincses; Péter Klivényi; Krisztina Bencsik; László Vécsei Journal: Int J Mol Sci Date: 2022-03-21 Impact factor: 5.923