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Abstract

Background: The strong association of multiple sclerosis (MS) and Epstein-Barr virus (EBV) infection raises the question whether there might be EBV seronegative patients with MS at all. Objective: To determine the rate of EBV seronegativity in a large and well-characterized cohort of patients with a clinically isolated syndrome (CIS) or early relapsing-remitting (RR)MS. Methods: Epstein-Barr nuclear antigen-1 (EBNA-1) antibodies were measured by a chemiluminescent assay (CLIA) in serum samples of 901 patients (median [interquartile range] age 33 [27-41] years, 69.9% females) with a CIS (n = 380) or early RRMS (n = 521) from the German National MS cohort. In EBNA-1 antibody seronegative patients, antibodies to the EBV viral capsid antigen (VCA) were measured by CLIA. EBNA-1 and VCA antibody double seronegative patients were analysed by an EBV immunoblot. Results: Antibodies to EBNA-1 were detected in 839 of 901 patients with CIS/RRMS. Of the 62 EBNA-1 antibody seronegative patients, 45 had antibodies to VCA. Of the 17 remaining patients, all had antibodies to EBV as detected by EBV immunoblot. Thus, all 901 (100%) patients with CIS/RRMS investigated in this study were EBV seropositive. Conclusions: The absence of EBV seronegativity in this large cohort of patients with early MS provides further evidence for a crucial role of EBV in MS and suggests that a negative EBV serology in a patient with suspected inflammatory central nervous system disease should alert clinicians to consider diagnoses other than MS. Disclosure SA reports no disclosures. BE reports no disclosures. BA received travel grants from Novartis, not related to this work. NH reports no disclosures. GA reports no disclosures. IRK reports no disclosures. M-MH received travel expenses from Bayer Health Care and honoraria for an advisory board from Merck Serono GmbH. LA reports no disclosures. FL serves as an advisory board member for Roche Pharma and has received travel grants from Teva Pharma. SG reports no disclosures. LK received compensation for serving on scientific advisory boards (Genzyme, Novartis Pharma); speaker honoraria and travel support (CSL Behring, Merck Serono, Roche, Novartis Pharma); research support (Biogen, Novartis Pharma). SGM received honoraria for lecturing, travel expenses for attending meetings, and/or financial research support from Almirall,

Associations between neurofilament light chain levels, disease activity and brain atrophy in progressive multiple sclerosis

“…A comparison of pNfL levels in the NEDA-3 and EDA-3 subgroups showed significant higher levels in the EDA-3 group (6.7 ± 2.48 vs 14.28 ± 6.03). These results are consistent with the findings of several studies 5,[22][23][24][25] and they seem to indicate that pNfL reflects disease activity measured by 3-domain NEDA-3 status. In addition, it may support ability of immunosuppressive DMTs to supress NfL.…”

“…This shows that BVL probably well captures the disease activity in PMS; similar results have been presented in a few studies with progressive MS (ref. [24][25][26][27] ). In fact, this allows us to conclude that an analysis with pNfL as the dependent variable may better quantify the association between pNfL and recent BVL and indicate whether pNfL and BVL may be somehow complementary.…”

“…Their role in progressive MS, where there is a particularly urgent need for sensitive valid biomarkers, is less clear. Several studies have shown that NfL levels in PMS are associated with current inflammatory activity 22,[24][25][26] , current disability (EDSS, MSFC) (ref. 6,22,25,26 ), future disability worsening and future brain and spinal cord atrophy.…”

“…Several studies have shown that NfL levels in PMS are associated with current inflammatory activity 22,[24][25][26] , current disability (EDSS, MSFC) (ref. 6,22,25,26 ), future disability worsening and future brain and spinal cord atrophy. A few studies have consistently shown NfL to be a marker of treatment response with immunosuppressive disease-modifying therapies 22,25,27 .…”

Neurofilaments in progressive multiple sclerosis: a systematic review

“…A number of studies (including 312 PMS patients) have reported that CSF or blood NFL (cNFL/bNFL) is higher in PMS compared to RRMS [4,5,[10][11][12][13][14][15][16][17][18][19], or that it increases more quickly in PMS [20]. Others, however, report that NFL is lower in PMS compared to RRMS [21][22][23] or controls [24].…”