Seroreactivity against lytic, latent and possible cross-reactive EBV antigens appears on average 10 years before MS induced preclinical neuroaxonal damage
Journal article, 2023
Background: Multiple sclerosis (MS) and presymptomatic axonal injury appear to develop only after an Epstein-Barr virus (EBV) infection. This association remains to be confirmed across a broad preclinical time range, for lytic and latent EBV seroreactivity, and for potential cross-reacting antigens. Methods: We performed a case-control study with 669 individual serum samples obtained before clinical MS onset, identified through cross-linkage with the Swedish MS register. We assayed antibodies against EBV nuclear antigen 1 (EBNA1), viral capsid antigen p18, glycoprotein 350 (gp350), the potential cross-reacting protein anoctamin 2 (ANO2) and the level of sNfL, a marker of axonal injury. Results: EBNA1 (latency) seroreactivity increased in the pre-MS group, at 15-20 years before clinical MS onset, followed by gp350 (lytic) seroreactivity (p=0.001-0.009), ANO2 seropositivity appeared shortly after EBNA1-seropositivity in 16.7% of pre-MS cases and 10.0% of controls (p=0.001).With an average lag of almost a decade after EBV, sNfL gradually increased, mainly in the increasing subgroup of seropositive pre-MS cases (p=8.10-5 compared with non-MS controls). Seropositive pre-MS cases reached higher sNfL levels than seronegative pre-MS (p=0.038). In the EBNA1-seropositive pre-MS group, ANO2 seropositive cases had 26% higher sNfL level (p=0.0026). Conclusions: Seroreactivity against latent and lytic EBV antigens, and in a subset ANO2, was detectable on average a decade before the appearance of a gradually increasing axonal injury occurring in the last decade before the onset of clinical MS. These findings strengthen the hypothesis of latent EBV involvement in the pathogenesis of MS.
MULTIPLE SCLEROSIS
VIROLOGY
Author
Daniel Jons
University of Gothenburg
Viktor Grut
Umeå University
Tomas Bergström
University of Gothenburg
Sahlgrenska University Hospital
Henrik Zetterberg
University of Gothenburg
Sahlgrenska University Hospital
Martin Biström
Umeå University
Martin Gunnarsson
Faculty of Medicine and Health
M Vrethem
Linköping University
Nicole Brenner
German Cancer Research Center (DKFZ)
Julia Butt
German Cancer Research Center (DKFZ)
Kaj Blennow
University of Gothenburg
Sahlgrenska University Hospital
Staffan Nilsson
University of Gothenburg
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
Ingrid Kockum
Karolinska Institutet
Tomas Olsson
Karolinska Institutet
Tim Waterboer
German Cancer Research Center (DKFZ)
Peter Sundström
Umeå University
Oluf Andersen
University of Gothenburg
Journal of Neurology, Neurosurgery and Psychiatry
0022-3050 (ISSN) 1468-330X (eISSN)
331868Subject Categories
Neurosciences
Neurology
Cancer and Oncology
DOI
10.1136/jnnp-2023-331868
PubMed
37802637