Soluble CD40L and interleukin-31: new candidate serum biomarkers that predict therapeutic response and relapses in MS

Although the roles of several cytokines and chemokines in multiple sclerosis (MS) are well established, their roles in MS lesions and evolution remain a matter of debate. MS is characterized by demyelination and variable degrees of axonal loss. The profound heterogeneity of MS is not only limited to the symptoms, but also to the neuroradiological and histological appearances of the lesions and the responses to therapy. Thinking about that, some cytokines have drawn attention as possible biomarkers for MS. CD40 is a membrane protein from the TNF-alpha receptor superfamily. Its ligand, CD40L, is expressed particularly on the membrane surface of activated TCD4 cells (TCD4+). CD40-CD40L expression can be measured on the cell surface and in a soluble form in peripheral blood and CSF. Some articles have also shown increased serum expression of soluble CD40L (sCD40L) in other demyelinating diseases, making it a possible biomarker. Studies using fingolimod, interferon (IFN) beta-1a, IFNb, natalizumab and glatiramer acetate decreased the concentrations of IL-31 and sCD40L in peripheral blood mononuclear cells. The researchers measured the circulating levels of several immunometabolic markers in patients demonstrating that higher levels of sCD40L were associated with a higher relapse rate and a greater risk of experiencing at least one relapse during the following year. In addition, some authors correlated not only the increasing levels of sCD40L with worsening clinical conditions, but with IL-31. IL-31 is mainly produced by TCD4+ and mast cells, it is released in inflammatory situations. So, we demonstrated that it is possible to consider sCD40L and IL-31 molecules as biomarkers of therapeutic response in MS, controlling and predicting new relapses. Given the large impact of sCD40L receptor signaling on the immune response, novel therapies may target the inhibition of the CD40-CD40L axis, possibly by modulating its responses.