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Background: Albeit several studies pointed out the pivotal role that CD4+T cells have in Multiple Sclerosis, the CD8+ T cells involvement in the pathology is still in its early phases of investigation. Proteasome degradation is the key step in the production of MHC class I-restricted epitopes and therefore its activity could be an important element in the activation and regulation of autoreactive CD8+ T cells in Multiple Sclerosis. Methodology/Principal Findings: Immunoproteasomes and PA28-αβ regulator are present in MS affected brain area and accumulated in plaques. They are expressed in cell types supposed to be involved in MS development such as neurons, endothelial cells, oligodendrocytes, macrophages/macroglia and lymphocytes. Furthermore, in a genetic study on 1262 Italian MS cases and 845 controls we observed that HLA-A*02+ female subjects carrying the immunoproteasome LMP2 codon 60HH variant have a reduced risk to develop MS. Accordingly, immunoproteasomes carrying the LMP2 60H allele produce in vitro a lower amount of the HLA-A*0201 restricted immunodominant epitope MBP111-119. Conclusion/Significance: The immunoproteasome LMP2 60HH variant reduces the risk to develop MS amongst Italian HLA-A* 02+ females. We propose that such an effect is mediated by the altered proteasome-dependent production of a specific MBP epitope presented on the MHC class I. Our observations thereby support the hypothesis of an involvement of immunoproteasome in the MS pathogenesis. [ABSTRACT FROM AUTHOR]

Background Month of birth has been associated in some studies with the susceptibility to develop Multiple Sclerosis (MS). However, only few studies have evaluated whether birth timing also affects disease progression. Objectives To assess whether season and month of birth are associated with disease progression in a large cohort of Italian patients. Methods Quantile regression was used to analyze the impact of each month and season of birth with all the others combined on the median Multiple Sclerosis Severity Score of 1866 MS patients. Results No significant temporal trend was found after adjustment for multiple comparisons. Conclusions Birth timing showed no association with MS progression in Italian patients. [ABSTRACT FROM AUTHOR]