Multiple sclerosis (MS) is a chronic, autoimmune disease of the central nervous system (CNS) characterized by consistent myelin and axonal damage that is mediated by autoreactive B- and T-cells. The role of B-cells in MS involves different cellular functions, including the production of autoantibody, antigen presentation to autoreactive T-cells and secretion of pro-inflammatory cytokines. Recent advances have led to the development of mAbs that effectively deplete B cells and target pathways essential for B-cell development. The pivotal role of B-cells in MS immunopathogenesis has been reinforced by the development of B cell-depleting monoclonal antibody (mAb), ocrelizumab that target the CD20 receptor on cells of the B cell lineage.
Ocrelizumab, is a humanized anti-CD20 mAb licensed on 2017, depletes circulating immature and mature B-cells through different way. Despite its clinical and radiological efficacy, ocrelizumab may increase the risk of reactivation of latent pathogenic viruses and contracting de novo infections, as result of a profound alteration of the immune response.
Given the infectious complications and the increasing use of ocrelizumab in MS, is necessary to identify predictive biomarkers that can provide better clinical management of patients and avoid possibly infectious adverse.
B cell activating factor (BAFF) and proliferation-inducing ligand (APRIL) are important cytokines involved in B-cell survival and activation. Moreover, CD40L is a costimulatory molecule involved in productive B-cell activation, antibody production, and isotype class switching.
The aim of the study is to evaluate the role of BAFF, APRIL and CD40L, as biomarkers of infectious risk during ocrelizumab treatment.
