Interleukin-31 and soluble CD40L: new candidate serum biomarkers that predict therapeutic response in multiple sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease that affects the central nervous system (CNS), varying from relatively benign to severely disabling. Although the roles of several cytokines and chemokines in MS are well established, their roles in MS lesions and evolution remain a matter of debate. Soluble CD40L (sCD40L) is a ligand that induces lymphocyte proinflammatory activity by stimulating the activation and maturation of B cells, promoting isotype switching and affinity hypermutation. Circulating sCD40L levels reflect activation of the CD40-CD40L complex. The interaction between CD40 and CD40L is of fundamental importance, suggesting their role in MS pathogenesis. Interleukin-31 (IL-31) is a proinflammatory cytokine that plays a role in allergies, autoimmune diseases, and is a major factor in several chronic inflammatory diseases. IL-31 triggers the JAK-STAT pathway in several different cell types, to induce proliferation and tissue remodeling in fibroblasts, epithelial cells, and endothelial cells. Some studies have described a correlation between these two cytokines and decreased serum levels of sCD40L and IL-31 after MS treatment, accompanied by a lower inflammatory response. In this review, we emphasize the possible correlation and positive feedback between IL31 and sCD40L in the MS proinflammatory response. We also describe the justification for this hypothesis and whether it is possible to investigate these cytokines as biomarkers of MS.

Altered expression of microRNAs and B lymphocytes during Natalizumab therapy in multiple sclerosis.

MicroRNAs (miRNAs) are a family of non-translated small ribonucleic acids (RNAs) measuring 21-25 nucleotides in length that play various roles in multiple sclerosis (MS). By regulating gene expression via either mediating translational repression or cleavage of the target RNA, miRNAs can alter the expression of transcripts in different cells, such as B lymphocytes, also known as B cells. They are crucial in the pathogenesis of MS; however, they have not been extensively studied during the treatment of some drugs such as natalizumab (NTZ). NTZ is a humanized immunoglobulin G4 antibody antagonist for integrin alpha 4 (α4) used in the treatment of MS. The drug reduces the homing of lymphocytes to inflammation sites. Integrin α4 expression on the cell surface of B cells is related to MS severity, indicating a critical component in the pathogenesis of the disease. NTZ plays an important role in modifying the gene expression in B cells and the levels of miRNAs in the treatment of MS. In this review, we have described changes in gene expression in B cells and the levels of miRNAs during NTZ therapy in MS and its relapse. Studies using the experimental autoimmune encephalomyelitis (EAE) model and those involving patients with MS have described changes in the levels of microRNAs in the regulation of proteins affected by specific miRNAs, gene expression in B cells, and certain functions of B cells as well as their subpopulations. Therefore, there is a possibility that some miRNAs could be studied at different stages of MS during NTZ treatment, and these specific miRNAs can be tested as markers of therapeutic response to this drug in future studies. Physiopathology, gene expression in B cells and their subpopulations can help understand this complex puzzle involving miRNAs and the therapeutic response of patients with MS.