Hypothesis: Another idea about the cause of MS.

Pender MP. CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis. Autoimmune Dis. 2012;2012:189096.

CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases such as multiple sclerosis. It also occurs in healthy blood relatives of patients with autoimmune diseases, suggesting it is genetically determined. Here it is proposed that this CD8+ (virus-killing) T-cell deficiency underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of Epstein-Barr virus (EBV) infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis. Autoimmunity is postulated to evolve in the following steps: (1) CD8+ T-cell deficiency, (2) primary EBV infection, (3) decreased CD8+ T-cell control of EBV, (4) increased EBV load and increased anti-EBV antibodies, (5) EBV infection in the target organ, (6) clonal expansion of EBV-infected autoreactive B cells in the target organ, (7) infiltration of autoreactive T cells into the target organ, and (8) development of ectopic lymphoid follicles in the target organ. It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection.

Here is yet another view on the causes of MS. The potential weakness is that we really are not sure to what extent there really is a CD8 deficiency in MS but the authors previous work has suggested a deficiency in the response to killing of EBV-infected B cells..

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  • Prof G,

    I thought you were a fan of EBV as a possible cause! Is Prof P's theory very different to your own ideas about EBV and it's role in MS?

  • I read the paper (looks a reasonable hypothesis for a layman like me).

    The way to address it seems similar to some of the ideas posted by Prof G. Is Prof Pender interested in collaborating on the Charcot Project?

    "There are potentially 3 ways to treat chronic autoimmune diseases by controlling EBV infection: (1) B-cell depletion with monoclonal antibodies; (2) boosting immunity to EBV; (3) antiviral drugs. B-cell depletion with rituximab eliminates not only EBV-infected B cells but also uninfected B cells, which normally confer protective immunity against infectious agents."

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