Editing Multiple sclerosis (section)

=== Epstein-Barr virus ===
As of 2022, the pathogenesis of MS, as it relates to [[Epstein–Barr virus|Epstein-Barr virus (EBV)]], is actively investigated, as are disease-modifying therapies; understanding of how risk factors combine with EBV to initiate MS is sought. Whether EBV is the only cause of MS might be better understood if an [[Epstein–Barr virus vaccine|EBV vaccine]] is developed and shown to prevent MS as well.<ref name="Aloisi20222"/>

Even though a variety of studies showed the connection between an EBV infection and a later development of multiple sclerosis, the mechanisms behind this correlation are not completely clear, and several theories have been proposed to explain the relationship between the two diseases. It is thought that the involvement of EBV-infected [[B cell|B-cells]] (B lymphocytes)<ref>{{cite journal | vauthors = Bar-Or A, Pender MP, Khanna R, Steinman L, Hartung HP, Maniar T, Croze E, Aftab BT, Giovannoni G, Joshi MA | title = Epstein-Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies | journal = Trends in Molecular Medicine | volume = 26 | issue = 3 | pages = 296–310 | date = March 2020 | pmid = 31862243 | pmc = 7106557 | doi = 10.1016/j.molmed.2019.11.003 }}</ref> and the involvement of anti-[[EBNA]] antibodies, which appear to be significantly higher in multiple sclerosis patients, play a crucial role in the development of the disease.<ref>{{cite journal | vauthors = DeLorenze GN, Munger KL, Lennette ET, Orentreich N, Vogelman JH, Ascherio A | title = Epstein-Barr virus and multiple sclerosis: evidence of association from a prospective study with long-term follow-up | journal = Archives of Neurology | volume = 63 | issue = 6 | pages = 839–844 | date = June 2006 | pmid = 16606758 | doi = 10.1001/archneur.63.6.noc50328 | doi-access = free }}</ref> This is supported by the fact that treatment against B-cells, e.g. [[ocrelizumab]], reduces the symptoms of multiple sclerosis: annual relapses appear less frequently and the disability progression is slower.<ref>{{cite journal | vauthors = Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L | title = Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis | journal = The New England Journal of Medicine | volume = 376 | issue = 3 | pages = 221–234 | date = January 2017 | pmid = 28002679 | doi = 10.1056/NEJMoa1601277 | s2cid = 205099904 | hdl = 2445/178507 | hdl-access = free }}</ref> A 2022 [[Stanford University]] study has shown that during an EBV infection, molecular mimicry can occur, where the immune system will produce antibodies against the [[EBNA]]1 protein, which at the same time is able to bind to GlialCAM in the myelin. Additionally, they observed a phenomenon which is uncommon in healthy individuals but often detected in multiple sclerosis patients – B-cells are trafficking to the brain and spinal cord, where they are producing oligoclonal antibody bands. A majority of these oligoclonal bands do have an affinity to the viral protein EBNA1, which is cross-reactive to GlialCAM. These antibodies are abundant in approximately 20–25% of multiple sclerosis patients and worsen the autoimmune demyelination which leads consequently to a pathophysiological exacerbation of the disease. Furthermore, the intrathecal oligoclonal expansion with a constant somatic hypermutation is unique in multiple sclerosis when compared to other neuroinflammatory diseases. In the study, there was also the abundance of antibodies with IGHV 3–7 genes measured, which appears to be connected to the disease progress. Antibodies which are IGHV3–7-based are binding with a high affinity to EBNA1 and GlialCAM. This process is actively thriving the demyelination. It is probable that B-cells, expressing IGHV 3–7 genes entered the CSF and underwent affinity maturation after facing GlialCAM, which led consequently to the production of high-affinity anti-GlialCAM antibodies. This was additionally shown in the EAE mouse model where immunization with EBNA1 lead to a strong B-cell response against GlialCAM, which worsened the EAE.<ref>{{cite journal | vauthors = Lanz TV, Brewer RC, Ho PP, Moon JS, Jude KM, Fernandez D, Fernandes RA, Gomez AM, Nadj GS, Bartley CM, Schubert RD, Hawes IA, Vazquez SE, Iyer M, Zuchero JB, Teegen B, Dunn JE, Lock CB, Kipp LB, Cotham VC, Ueberheide BM, Aftab BT, Anderson MS, DeRisi JL, Wilson MR, Bashford-Rogers RJ, Platten M, Garcia KC, Steinman L, Robinson WH | title = Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM | journal = Nature | volume = 603 | issue = 7900 | pages = 321–327 | date = March 2022 | pmid = 35073561 | pmc = 9382663 | doi = 10.1038/s41586-022-04432-7 | bibcode = 2022Natur.603..321L }}</ref>