Glatiramer Acetate modulates ion channels expression and calcium homeostasis in B cell of patients with relapsing-remitting multiple sclerosis

To investigate the effects of Glatiramer Acetate (GA) on B cells by an integrated computational and experimental approach. GA is an immunomodulatory drug approved for the treatment of multiple sclerosis (MS). GA effect on B cells is yet to be fully elucidated. We compared transcriptional profiles of B cells from treatment-naïve relapsing remitting MS patients, treated or not with GA for 6 hours in vitro , and of B cells before and after six months of GA administration in vivo . Microarrays were analyzed with two different computational approaches, one for functional analysis of pathways (Gene Set Enrichment Analysis) and one for the identification of new drug targets (Mode-of-action by Network Analysis). GA modulates the expression of genes involved in immune response and apoptosis. A differential expression of genes encoding ion channels, mostly regulating Ca 2+ homeostasis in endoplasmic reticulum (ER) was also observed. Microfluorimetric analysis confirmed this finding, showing a specific GA effect on ER Ca 2+ concentration. Our findings unveils a GA regulatory effect on the immune response by influencing B cell phenotype and function. In particular, our results highlight a new functional role for GA in modulating Ca 2+ homeostasis in these cells.