Introduction/Objectives:
Natalizumab (Tysabri) is a monoclonal antibody used in the treatment of multiple sclerosis (MS). This humanized antibody binds directly at the alpha 4-integrin subunit of the adhesion molecule (AM) very late activation antigen-4 (VLA-4) and thus leads to an inhibition of immune cell extravasation across the blood brain barrier. This consecutively results in a reduced inflammation of the central nervous system. Our objective was to study the effect of Natalizumab on soluble cell AMs in peripheral blood of patients before and 3 months after onset of Natalizumab treatment.
Participants, Materials/Methods:
We determined serum concentration levels of four different AMs (soluble intercellular adhesion molecule-1, -2, -3 [sICAM-1, -2, -3] and vascular cell adhesion molecule-1 [sVCAM-1]) by using fluorescent bead immunoassay and enzyme linked immunosorbent assay (ELISA). Blood was sampled from 15 MS patients before and 3 months after onset of Natalizumab treatment.
Results:
A significant decrease was found in all patients for the median of sICAM-3 serum concentration levels (before therapy: 100 ng/ml; after 3 months: 61 ng/ml; P < 0.001) and sVCAM-1 (before therapy: 580 ng/ml; after 3 months: 216 ng/ml; P < 0.001) levels 3 months after onset of Natalizumab treatment. In contrast, serum levels of soluble ICAM-1 (before therapy: 452 ng/ml; after 3 months: 479 ng/ml) and ICAM-2 (before therapy: 263 U/ml; after 3 months: 242 U/ml) remained unchanged.
Conclusions:
We were able to show a differential effect after 3 months of natalizumab treatment with decreased serum levels in all investigated MS patients in two of the four investigated AMs (sICAM-3 and sVCAM-1).
VCAM-1 is the ligand of VLA-4. We therefore conclude that the decrease of sVCAM-1 might be a result of natalizumab mediated blocking of VLA-4. Alternatively, the decrease of sVCAM-1 in conjunction with the decrease of sICAM-3 might also be due to the anti-inflammatory effects of Natalizumab.
This study was supported by Biogen-Idec Austria
