Tomas Uher1, Mason McComb2, Shery Galkin2, Barbora Srpova1, Johanna Oechtering3, Christian Barro3, Michaela Tyblova1, Niels Bergsland4, Jan Krasensky5, Michael Dwyer6, Eva Kubala Havrdova1, Helena Posova7, Manuela Vaneckova5, Robert Zivadinov8, Dana Horakova1, Jens Kuhle3, Murali Ramanathan9. 1. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic. 2. Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA. 3. Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. 4. Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, The State University of New York, Buffalo, NY, USA/IRCCS, Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy. 5. Department of Radiology, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic. 6. Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, The State University of New York, Buffalo, NY, USA. 7. Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic. 8. Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, The State University of New York, Buffalo, NY, USA/Center for Biomedical Imaging, Clinical and Translational Science Institute, University at Buffalo, The State University of New York, Buffalo, NY, USA. 9. Department of Pharmaceutical Sciences, The State University of New York, Buffalo, NY, USA/Department of Neurology, The State University of New York, Buffalo, NY, USA.
Abstract
BACKGROUND: Increased blood brain barrier (BBB) permeability, CNS inflammation and neuroaxonal damage are pathological hallmarks in early multiple sclerosis (MS). OBJECTIVE: To investigate the associations of neurofilament light chain (NfL) levels with measures of BBB integrity and central nervous system (CNS) inflammation in MS during the first demyelinating event. METHODS: Blood and cerebrospinal fluid (CSF) were obtained from 142 MS (McDonald 2017) treatment-naive patients from the SET study (63% female; age: 29.7 ± 7.9 years) following the disease onset. NfL, albumin, immunoglobulin G (IgG), and immunoglobulin M (IgM) levels were measured in CSF and blood samples. Albumin quotient was computed as a marker of BBB integrity. Immune cell subset counts in CSF were measured using flow cytometry. MS risk factors, such as Human leukocyte antigen DRB1 locus gene (HLA DRB1)*1501, anti-Epstein-Barr virus (EBV) antibodies, and 25-hydroxy vitamin D3, were also measured. RESULTS: Higher serum NfL (sNfL) levels were associated with higher albumin quotient (p < 0.001), CSF CD80+ (p = 0.012), and CD80+ CD19+ (p = 0.015) cell frequency. sNfL levels were also associated with contrast-enhancing and T2 lesions on brain magnetic resonance imaging (MRI; all p ⩽ 0.001). Albumin quotient was not associated with any of the MS risk factors assessed. sNfL levels were associated with anti-EBV viral capsid antigen (VCA) IgG levels (p = 0.0026). CONCLUSION: sNfL levels during the first demyelinating event of MS are associated with greater impairment of BBB integrity, immune cell extravasation, and brain lesion activity on MRI.
BACKGROUND: Increased blood brain barrier (BBB) permeability, CNS inflammation and neuroaxonal damage are pathological hallmarks in early multiple sclerosis (MS). OBJECTIVE: To investigate the associations of neurofilament light chain (NfL) levels with measures of BBB integrity and central nervous system (CNS) inflammation in MS during the first demyelinating event. METHODS: Blood and cerebrospinal fluid (CSF) were obtained from 142 MS (McDonald 2017) treatment-naive patients from the SET study (63% female; age: 29.7 ± 7.9 years) following the disease onset. NfL, albumin, immunoglobulin G (IgG), and immunoglobulin M (IgM) levels were measured in CSF and blood samples. Albumin quotient was computed as a marker of BBB integrity. Immune cell subset counts in CSF were measured using flow cytometry. MS risk factors, such as Human leukocyte antigen DRB1 locus gene (HLA DRB1)*1501, anti-Epstein-Barr virus (EBV) antibodies, and 25-hydroxy vitamin D3, were also measured. RESULTS: Higher serum NfL (sNfL) levels were associated with higher albumin quotient (p < 0.001), CSF CD80+ (p = 0.012), and CD80+ CD19+ (p = 0.015) cell frequency. sNfL levels were also associated with contrast-enhancing and T2 lesions on brain magnetic resonance imaging (MRI; all p ⩽ 0.001). Albumin quotient was not associated with any of the MS risk factors assessed. sNfL levels were associated with anti-EBV viral capsid antigen (VCA) IgG levels (p = 0.0026). CONCLUSION: sNfL levels during the first demyelinating event of MS are associated with greater impairment of BBB integrity, immune cell extravasation, and brain lesion activity on MRI.
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