Methylome profiling of B and T cells along multiple sclerosis disease progression: a pilot study
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Multiple sclerosis (MS) is a chronic, inflammatory, autoimmune and neurodegenerative disease characterized by the infiltration of autoreactive immune cells into the central nervous system that leads to axonal damage, demyelination, and ultimately, neurodegeneration. The aetiology of MS is still unknown, but strong scientific evidence points to a complex interaction between genetic and environmental factors mediated by epigenetics. One of the most studied epigenetic mechanisms is the methylation of DNA, which consists of adding a methyl group to a naked cytosine. Alterations in the DNA methylation profile have been associated with pathogenic events, including MS.
This doctoral thesis studies the complete methylome of two immune cells closely involved in MS, memory B cells and regulatory T cells. In brief, recently diagnosed MS patients displayed global DNA hypomethylation in both immune cells, while MS patients at later stages of the disease exhibited a remarkable global DNA hypermethylation. Among the differentially methylated genes studied, PTGFRN, IL21R, NOS1, OSBP2, and MIR181C showed changes at the RNA level in memory B cells at diagnosis, while ECEL1P2 did so in regulatory T cells. At later stages of the disease, differential expression of MIR29A, MIR30D, MIR26A1, MIR92B, MIR150 and MIR193A was detected in memory B cells. Due to their neuroprotective role in MS, miR-29a, miR-30d and miR-26a qualify as promising candidates for future epigenetic interventions
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