Tu107 - Increased Monocyte Activity in Patients with Primary Progressive Multiple Sclerosis

Background. Emerging evidence suggests a prominent role of the innate immune system in the pathogenesis of multiple sclerosis (MS). With this study, we therefore investigated monocyte prevalence and activation in patients with relapsing remitting MS (RRMS) and primary progressive MS (PPMS).

Methods. Peripheral blood monocytes from healthy controls (n = 35), untreated patients with RRMS (n = 35), untreated patients with PPMS (n = 38), and patients with RRMS treated with ofatumumab (n = 17), dimethyl fumarate (n = 20) or alemtuzumab (n = 15) were analyzed by flow cytometry. Classical monocytes were defined as CD14⁺CD16^-, non-classical monocytes as CD14⁺CD16⁺, and activated monocytes as CD40⁺.

Results. This analysis showed an increased absolute count of classical monocytes in blood in patients with PPMS compared to healthy controls and, furthermore that the activation of both classical and non-classical monocytes in patients with PPMS was increased. No difference in monocyte phenotype or activation was observed in patients with RRMS compared to healthy controls. Following treatment of patients with RRMS with either of the three disease-modifying therapies included, the activation of non-classical monocytes was reduced.

Conclusion. Altogether, our data provide evidence of increased blood monocyte counts and activation in patients with PPMS but not in RRMS. Furthermore, we find that the activity of blood monocytes is reduced by various disease-modifying therapies. Consistent with previous findings, our study therefore indicates an involvement of innate immunity in the pathogenesis of progressive MS.