Seroreactivity against lytic, latent and possible cross-reactive EBV antigens appears on average 10 years before MS induced preclinical neuroaxonal damage
Artikel i vetenskaplig tidskrift, 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
Författare
Daniel Jons
Göteborgs universitet
Viktor Grut
Umeå universitet
Tomas Bergström
Göteborgs universitet
Sahlgrenska universitetssjukhuset
Henrik Zetterberg
Göteborgs universitet
Sahlgrenska universitetssjukhuset
Martin Biström
Umeå universitet
Martin Gunnarsson
Faculty of Medicine and Health
M Vrethem
Linköpings universitet
Nicole Brenner
Deutsches Krebsforschungszentrum (DKFZ)
Julia Butt
Deutsches Krebsforschungszentrum (DKFZ)
Kaj Blennow
Göteborgs universitet
Sahlgrenska universitetssjukhuset
Staffan Nilsson
Göteborgs universitet
Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik
Ingrid Kockum
Karolinska Institutet
Tomas Olsson
Karolinska Institutet
Tim Waterboer
Deutsches Krebsforschungszentrum (DKFZ)
Peter Sundström
Umeå universitet
Oluf Andersen
Göteborgs universitet
Journal of Neurology, Neurosurgery and Psychiatry
0022-3050 (ISSN) 1468-330X (eISSN)
331868Ämneskategorier
Neurovetenskaper
Neurologi
Cancer och onkologi
DOI
10.1136/jnnp-2023-331868
PubMed
37802637