Rodriguez, Moses

The pathogenesis of multiple sclerosis (MS) remains elusive. Recent reports advocate greater involvement of B cells and immunoglobulins in the initiation and propagation of MS lesions at different stages of their ontogeny. The key role of B cells and immunoglobulins in pathogenesis was initially identified by studies in which patients whose fulminant attacks of demyelination did not respond to steroids experienced remarkable functional improvement following plasma exchange. The positive response to Rituximab in Phase II clinical trials of relapsing-remitting MS confirms the role of B cells. The critical question is how B cells contribute to MS. In this paper, we discuss both the deleterious and the beneficial roles of B cells and immunoglobulins in MS lesions. We provide alternative hypotheses to explain both damaging and protective antibody responses.

Background: Axonal damage and inflammatory demyelination both occur in multiple sclerosis (MS). Some studies suggest that statins, through pleiotropic effects, reduce inflammatory episodes and protect neurons. However, other studies suggest statins have disparate impacts on these pathologic processes. Objective: The objective of this study was to assess disability progression in MS patients receiving statin therapy. Methods: We performed a retrospective medical record review of an established population-based MS prevalence cohort in Olmsted County, Minnesota, comparing disability progression between patients receiving statins and controls. Results: Duration of statin use ranged from 1.9 to 20.3 years with a mean and standard deviation of 6.8 ± 4 years. Years between assessments ranged from 0.6 to 8.2 (75% of patients having intervals >6.4 years). The median (interquartile range) absolute change of disability among the statin group was 0 (0 to +1), compared with +0.5 (0, +1) in the no-statin group. Distributions were not significantly different ( p = 0.39). The mean (standard deviation) absolute change of disability scores among the statin group was +0.69 (+1.49), not significantly different from +0.61 (+1.31) in the no-statin group. Likewise, annualized disability scores did not differ significantly ( p = 0.23). Eighteen (40%) patients worsened by 1.0 or more on Expanded Disability Status Scale (EDSS) in the statin group and 36 (40%) in the no-statin group ( p = 0.85, chi-squared test). Conclusions: In this cohort, disability progression did not differ between those receiving statin therapy and controls. These findings support the hypothesis that statins, in doses currently prescribed for hyperlipidemia, do not affect the long-term course of MS.

ABSTRACTTransgenic expression of the RNA-dependent RNA polymerase 3Dpolinhibited infection of Theiler's murine encephalitis virus (TMEV), a picornavirus from which it was derived. Here, we infected 3Dpoltransgenic mice with another picornavirus, as well as an alphaherpesvirus and a rhabdovirus. 3Dpoltransgenic FVB mice had significantly lower viral loads and survived longer after infection with all three types of viruses than nontransgenic FVB mice. Viral inhibition among three different types of virus by transgenic 3Dpolsuggests that the mechanism of action is not the direct interference with picornaviral 3Dpolbut instead may be the changing of host cells to an antiviral state before or after viral infection occurs, as basal interferon levels were higher in 3Dpoltransgenic mice before infection. Further study of this mechanism may open new possibilities for future antiviral therapy.

The RNA-dependent RNA-polymerase,3Dpol, is an essential component in the picornavirus genome for the replication of single stranded RNA. However, transgenic expression of3Dpolin mice has antiviral effects. Here, we discuss the structure and function of3Dpolduring picornavirus replication, we review the evidence and consequence of a host immune response to epitopes in3Dpolafter picornavirus infection, highlight data showing the antiviral effects of transgenic3Dpolfrom Theiler's murine encephalomyelitis virus (TMEV), and discuss potential mechanisms by which3Dpolis causing this antiviral effect in mice.