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The pathology of relapsing-remitting multiple sclerosis (RR-MS) is largely attributed to activated autoreactive effector T lymphocytes. The influence of microRNAs on the immune response has been shown to occur in different pathways of lymphocyte differentiation and function. Here, the expression of the miRNAs miR-15a/16-1 in PBMC, CD4+, and CD8+ from RR-MS patients has been investigated. BCL2, a known miR-15a/16-1 target, has also been analyzed. The results have shown that miR-15a/16-1 is downregulated in CD4+ T cells, whereas BCL2 is highly expressed in RR-MS patients only. Our data suggest that miR-15a/16-1 can also modulate the BCL2 gene expression in CD4+ T cells from RR-MS patients, thereby affecting apoptosis processes. [ABSTRACT FROM AUTHOR]

Background: The molecules that provide access to activated T cells in the CNS, including chemokines, have been considered to be a crucial step in the pathogenesis of multiple sclerosis (MS). Aims: In this study, we investigated serial serum chemokine levels in patients with relapsing-remitting MS over 1 year and the association of these chemokine levels with treatment regimens, lesions on MRI and patients' characteristics. Methods: Serum CXCL9, CXCLIO, CCL2, CCL4 and CCL5 levels were evaluated using ELISA every 2 months for a year in 28 healthy controls and 28 MS patients during their treatment with interferon (IFN)-ß. Patients under-went MRI and were evaluated using the Expanded Disability Status Scale (EDSS) at the first and final evaluations. Results: CXCL1 0 serum levels were higher in MS patients compared with controls, were positively correlated with T2 lesions on MRI and were slightly increased during relapses. Treatment with IFNß-1a or IFNß-lb was associated with increased CXCL1O levels when evaluated more than 36 hours after subcutaneous injection. The CXCL9 levels were higher after MS relapse. There was significant variability in CCL4 and CCL5 levels in the serial evaluations, associated with gender and treatment. CCL2 levels were higher in treated MS patients than healthy controls, particularly among those patients with a stable form of the disease. Conclusion: Serum is a feasible resource for searching for an immunological marker in MS. Peripheral chemokine levels correlated in different ways with IFNß therapy and with disease and patient characteristics. Clinical trial registration number: 1SRCTN45526724. [ABSTRACT FROM AUTHOR]

High dose immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) induces prolonged clinical remission in multiple sclerosis (MS) patients. However, how patient immune profiles are associated with clinical outcomes has not yet been completely elucidated. In this study, 37 MS patients were assessed for neurological outcomes, thymic function and long-term immune reconstitution after AHSCT. Patients were followed for a mean (SD) of 68.5 (13.9) months post-transplantation and were retrospectively clustered into progression- and non-progression groups, based on Expanded Disease Status Scale (EDSS) outcomes at last visit. After AHSCT, both patient groups presented increased regulatory T -cell subset counts, early expansion of central- and effector-memory CD8 + T -cells and late thymic reactivation. However, the non-progression group presented early expansion of PD-1 + CD8 + T -cells and of PD-1-expressing CD19 + B-cells. Here, we suggest that along with increased numbers of regulatory T -cell subsets, PD-1 inhibitory signaling is one possible immunoregulatory mechanism by which AHSCT restores immune tolerance in MS patients. [ABSTRACT FROM AUTHOR]