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Natalizumab Promotes Activation of Peripheral Monocytes in Patients With Multiple Sclerosis
Esther S Frisch1, Darius Häusler1, Martin S Weber2
1From the Department of Neuropathology (E.S.F., D.H., M.S.W.), University Medical Center; Department of Neurology (E.S.F., M.S.W.), University Medical Center; and Fraunhofer-Institute for Translational Medicine and Pharmacology ITMP (D.H., M.S.W.), Göttingen, Germany.
Objectives:
Natalizumab (NTZ), a monoclonal antibody against very late antigen-4 (VLA-4), is one of the most efficient therapies to prevent acute relapses in multiple sclerosis (MS). VLA-4 is the key adhesion molecule for peripheral immune cells, especially lymphocytes to enter the CNS. While its blockade thus virtually abrogates CNS infiltration of these cells, long-term exposure to natalizumab may also affect immune cell function.
Methods:
In this study, we report that in patients with MS, NTZ treatment is associated with an enhanced activation status of peripheral monocytes.
Results:
Expression of 2 independent activation markers, CD69 and CD150, was significantly higher on blood monocytes from NTZ-treated patients when compared with those from matched untreated patients with MS, while other properties such as cytokine production remained unchanged.
Discussion:
These findings consolidate the concept that peripheral immune cells remain fully competent on NTZ treatment, an excellent asset rare among MS treatments. However, they also suggest that NTZ may exert nondesirable effects on the progressive aspect of MS, where myeloid cells and their chronic activation are attributed a prominent pathophysiologic role.
