Frequent intrathecal production of antibodies to the viral capsid antigen of Epstein-Barr virus in patients with central nervous system post-transplant lymphoproliferative disorder

Otto, Carolin; Radbruch, Helena; Wilken, D.; Lietzow, Tatjana; Steinhagen, Katja; Grage-Griebenow, Evelin; Brünneck, Ann-Christin von; Jarius, Sven; Hofmann, Jörg; Pache, Florence; Ruprecht, Klemens

doi:10.1016/j.jneuroim.2022.577902

Cited by 1 publication

(1 citation statement)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…How many of these primary infections manifested as IM is not known. EBNA1 is a latency antigen, described as a dominant antigen in serological studies in clinical 26 and presymptomatic MS. 18 27 VCA antibody reactivity, however, has been associated with other diseases, such as systemic lupus erythematosus, 28 post-transplantation lymphoproliferative disorders 29 and Hodgkin's lymphoma. 30 We also evaluated gp350 as a major pre-MS lytic antigen with an established neutralising capacity that elicits persistent immunoreactivity in convalescence 10 years after IM compared with asymptomatic primary infection.…”

Section: Multiple Sclerosismentioning

confidence: 99%

Seroreactivity against lytic, latent and possible cross-reactive EBV antigens appears on average 10 years before MS induced preclinical neuroaxonal damage

Jons,

Grut,

Bergström

et al. 2023

J Neurol Neurosurg Psychiatry

View full text Add to dashboard Cite

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=8.10−5compared 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.

show abstract