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Seroreactivity against lytic, latent and possible cross-reactive EBV antigens appears on average 10 years before MS induced preclinical neuroaxonal damage
- Publication Year :
- 2024
-
Abstract
- BackgroundMultiple 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.MethodsWe 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.ResultsEBNA1 (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).ConclusionsSeroreactivity 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.<br />Funding Agencies|Swedish Government [ALFGBG- 715986, 2017- 00915]; County Councils [ALFGBG- 772071, AF- 742881]; Research Foundation of the Gothenburg MS Society; Bjornsson Research Foundation; Gothenburg, Sweden; Gothenburg Society of Medicine; Visare Norr Fund; Northern County Councils Regional Federation; Research and Development Unit; Region Jaemtland Haerjedalen; Research Fund for Clinical Neuroscience at the University Hospital of Northern Sweden; Oskarfonden; NEURO Sweden; Swedish Research Council [ALFGBG- 772071]; European Research Council [ALFGBG- 715986, 2018- 02532]; Swedish State Support for Clinical Research [681712]; Alzheimer Drug Discovery Foundation-USA [101053962, 860197]; AD Strategic Fund and the Alzheimers Association [ALFGBG- 71320, 201809-2016862, RDAPB- 201809- 2016615]; Olav Thon Foundation; Erling- Persson Family Foundation; Stiftelsen foer Gamla Tjaenarinnor; Hjaernfonden-Sweden [ADSF- 21- 831376- C, UKDRI- 1003]; European Union [ADSF- 21- 831381- C]; European Union Joint Programme-Neurodegenerative Disease Research [ADSF- 21- 831377- C]; UK Dementia Research Institute at University College London [FO2019- 0228]; Swedish Research Council [FO2017- 0243]; Swedish Alzheimer Foundation [JPND2021- 00694]; European Union Joint Program for Neurodegenerative Disorders [JPND2019- 466- 236]; US National Institutes of Health [1R01AG068398- 01]; Alzheimers Association 2021 Zenith Award [ZEN- 21- 848495]; Swedish Brain Foundation; Knut and Alice Wallenberg Foundation; Margaretha af Ugglas Foundation; European Horizon [733161]; Swedish Research Foundation [2020- 01638]
Details
- Database :
- OAIster
- Notes :
- application/pdf, English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1428119501
- Document Type :
- Electronic Resource
- Full Text :
- https://doi.org/10.1136.jnnp-2023-331868