Younis S, Moutusy SI, Rasouli S, Jahanbani S, Pandit M, Wu X, Acharya S, Sharpe O, Wijeratne TU, Harris ML, Yang EY, Chaichian Y, Parsafar S, Baker MC, Harley JB, Meffre E, Steinman L, Marshak-Rothstein A, James JA, Martinez OM, Utz PJ, Orange DE, Lanz TV, Robinson WH.Sci Transl Med. 2025;17(824):eady0210. doi: 10.1126/scitranslmed.ady0210.
I have been saying for years that EBV is more than MS so thinking that EBV is causal only for MS does’nt make sense. There is evidence for the involvement of EBV in loads of other suspected autoimmune conditions. Lupus is an suspected autoimmune disease where there are antibodies that target multiple different targets around the body. Having suggested that EBV was a cause of MS due to cross-reactive antibodies they turn their attention to Lupus. I have always said that we can learn from other conditions.
Baker D, Pryce G, Amor S, Giovannoni G, Schmierer K. Learning from other autoimmunities to understand targeting of B cells to control multiple sclerosis. Brain. 2018 ;141(10):2834-2847.
So they say “Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by antinuclear antibodies (ANAs) (Antibodies against elements in the nucleus of cells e.g. DNA). Epstein-Barr virus (EBV) infection has been epidemiologically associated with SLE, yet its role in pathogenesis remains incompletely defined. Here, we developed an EBV-specific single-cell RNA-sequencing platform and used it to demonstrate that EBV infection reprograms autoreactive antinuclear antigen B cells to drive autoimmunity in SLE. We demonstrated that, in SLE, EBV+ B cells are predominantly CD27+CD21low memory B cells (OK abit of a NSS moment here..We have been saying this for years…it is well known that memory B cells infects and drives the differentiation of B cells into memory B cells) that are present at increased frequencies and express ZEB2, TBX21 (T-bet), and antigen-presenting cell transcriptional pathways (They say that memory B cells present antigen ok… another NSS moment). Integrative analysis of chromatin immunoprecipitation sequencing (ChIP-seq), assay for transposase-accessible chromatin sequencing (ATAC-seq), and RNA polymerase II occupancy data revealed EBV nuclear antigen 2 (EBNA2) binding at the transcriptional start sites and regulatory regions of CD27, ZEB2, and TBX21, as well as the antigen-presenting cell genes demonstrated to be up-regulated in SLE EBV+ B cells (See above). We expressed recombinant antibodies from SLE EBV+ B cells and demonstrated that they bind prototypical SLE nuclear autoantigens, whereas those from healthy individuals do not. (Em) We further found that SLE EBV+ B cells can serve as antigen-presenting cells to drive activation of T peripheral helper cells with concomitant activation of related EBV– antinuclear double-negative 2 B cells and plasmablasts (Antigen presenting infected B cells activte non infected B cells). Our results provide a mechanistic basis for EBV being a driver of SLE through infecting and reprogramming nuclear antigen-reactive B cells to become activated antigen-presenting cells with the potential to promote systemic disease-driving autoimmune responses.
The editors take
Editor says ” Younis et al. provide evidence…….that infected B cells were transcriptionally distinct from their uninfected counterparts (NSS). EBV-infected B cells exhibited features associated with antigen presentation, and this programming seemed likely to be directly driven by the EBV protein EBNA2. These EBV-infected B cells with antigen-presenting abilities had the capacity to activate autoreactive helper T cells, setting off a chain reaction where those T cells could activate other autoreactive B cells, including uninfected ones……These data suggest that EBV infects and reprograms autoreactive B cells that, in turn, drive the systemic autoimmune response in SLE.
Gorochov & Mathian Transl Med.;17:eaec 0501i say “Younis et al. could not determine whether EBV reactivation is a driver of SLE flares or a consequence of them and whether the “driver” B cell phenotype is Lupus-specific”.
They hope that B cell directed CAR-T therapy can root out all the EBV infected B cells….maybe but we know from HSCT that people get a new immune system and they get re-infected with EBV and show B cell expansion…but more evidence for for anti-EBV studies..ProfG will be happy.
CoI None
Disclaimer My views.
Source: multiple-sclerosis-research.org