Natalizumab Therapy Modulates miR 155, miR 26a and Proinflammatory Cytokine Expression in MS Patients
MicroRNAs fine tune the regulation of Th1/Th17 lymphocyte subsets in multiple sclerosis. We investigated the expression of miRNAs (previously associated with mycobacterial and viral infections) in MS patients and healthy donors (HD) following 6 months natalizumab therapy. In addition, Th1/Th17 cytokines and the presence of anti EBNA1/VCA IgG in MS patients with different pattern of miRNA expression have been evaluated. MiR 155, miR 26a, miR 132, miR 146a and Th1/Th17 cytokines expression was detected by RT real time PCR; moreover anti EBNA1 and VCA IgG titres were measured by ELISA. We observed an up regulation of miR 155 (p value 0.009) and miR 132 (p value 0.04) in MS patients compared to HD. In MS patients, IL 17a (p 0.037) IFN g (p 0.012) and TNFa (p 0.015) but not IL 6 were over expressed compared to HD. Two different miRNAs patterns associated to the expression of different cytokines were observed in the MS cohort. Moreover, a down regulation of miR 155 and miR 26a was seen in MS patients during and after natalizumab therapy. MS patients that over expressed miR 155 showed a higher EBNA1 IgG titer than MS patients with high levels of miR 26a. In conclusions the expression of particular miRNAs modulates the pro inflammatory cytokine expression and the humoral response against EBV and this expression is natalizumab regulated.
PloS one