In the case of artificial light, it will be important to ensure that the light includes the UVB wavelengths (280C320?nm) needed to stimulate vitamin D synthesis in the skin. Does EBV vaccination protect against BD? EpsteinCBarr virus\induced infectious mononucleosis, but not asymptomatic EBV infection, in healthy EBV\seronegative young adults is effectively prevented by vaccination with recombinant EBV gp350 glycoprotein. 87 The subjects who were vaccinated developed anti\gp350 antibodies, which most likely provided the protective effect because monoclonal anti\gp350 antibody neutralises EBV infectivity of B cells. 88 The efficacy of this vaccine Secalciferol is limited because it protects only B cells, and not epithelial cells, from infection. and to be prevented by Secalciferol vaccination against EBV in early childhood. Exposure to sunlight or appropriate artificial light should also be beneficial in BD by augmenting CD8+ T\cell control of EBV infection. strong class=”kwd-title” Keywords: autoimmune, bipolar disorder, CD8 T cell, EpsteinCBarr virus, sunlight, T\cell therapy Abstract This article proposes the novel hypothesis that bipolar disorder (BD) is a chronic autoimmune disease caused by EpsteinCBarr virus (EBV) infection of autoreactive B cells, which accumulate in the brain where they facilitate an autoimmune attack on brain components such as the NMDA receptor. It is postulated that the accumulation of EBV\infected autoreactive B cells in the brain is a consequence of a genetically determined defect in the ability of CD8+ T cells to control EBV infection. According to the hypothesis, BD should be able to be treated by EBV\specific T\cell therapy and to be prevented by vaccination Secalciferol against EBV early in life. Introduction Bipolar disorder (BD) is a chronic disease characterised by episodes of major depression and episodes of mania or hypomania, 1 with a worldwide prevalence of 2.4% when subthreshold BD is included. 2 The cause of BD is unknown. The concordance rate of BD in monozygotic twins is 40C70%, 3 indicating that genetic factors have a major role in the development of the disease. Given that this concordance rate is substantially less than 100%, environmental factors are also likely to make a significant contribution to the pathogenesis of the disease. There is some evidence that BD is a chronic autoimmune disease. I have previously hypothesised that all human chronic autoimmune diseases are caused by EpsteinCBarr virus (EBV) infection of autoreactive B cells, which accumulate in the target organ where they provide costimulatory survival signals to autoreactive T cells and differentiate into plasma cells producing pathogenic autoantibodies. 4 Here, I hypothesise that BD is an EBV\driven chronic autoimmune disease. The hypothesis gives rise to predictions that can be tested. A crucial prediction derived from the hypothesis is that BD should be able to be treated by EBV\specific T\cell therapy and to be prevented by vaccination against EBV early in life. Exposure to sunlight or appropriate artificial light should also be beneficial in BD by augmenting CD8+ T\cell control of EBV infection. The article will proceed through the following sections: (1) the pathophysiology of BD; (2) evidence that BD is an autoimmune disease; (3) introduction to EBV; (4) introduction to EBV\infected autoreactive B\cell hypothesis of Secalciferol autoimmunity; (5) evidence for a role of EBV in the pathogenesis of BD; (6) evidence for a role of CD8+ T\cell deficiency in BD; (7) the benefit of sunlight; (8) the role of stress; (9) proposed hypothesis for the development of BD; (10) testing the hypothesis, including the implications for immunotherapy and phototherapy; NUPR1 and (11) conclusion. Pathophysiology of BD The pathophysiology of BD is complex and incompletely understood. Functional magnetic resonance imaging studies of emotional processing in BD have demonstrated underactivity of the ventrolateral prefrontal cortex and Secalciferol overactivity in the limbic regions, thalamus and basal ganglia. 5 Diffusion tensor imaging studies of the brain in BD have shown decreased fractional anisotropy, indicating decreased structural connectivity, in the corpus callosum. 6 , 7 Histological studies of the brain in BD have revealed a decrease in hippocampal N\methyl\D\aspartate (NMDA) receptors with open ion channels, but no.
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- 1995) strains of were used for protein expression and cloning, respectively
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