The mean variation of the anti-HHV-6A/B IgG titers (around 20% of increase or decrease) was lower than the mean variation of the anti-HHV-6A/B IgM titers (more than 30% of increase or decrease); no statistical significant correlations were found between the clinical response and the variation of the anti-HHV-6A/B IgM titers after two years with the different DMTs, only a trend for natalizumab when we compared MS patients with increases or decreases >30% (37.5% vs. 69.2%, respectively, p = 0.089). Here, CD40LG is linked to myeloid sarcoma.