In this study, we compared BTK expression and phosphorylation in blood B cell subsets from control and clinical MS groups; these groups included clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS) before and after treatment with natalizumab (NTZ; anti–VLA-4 antibody), secondary progressive MS (SPMS), and primary progressive MS (PPMS). Here, BTK is linked to primary progressive multiple sclerosis.