Aktuelle Neurologie 2009; 36 - P675
DOI: 10.1055/s-0029-1238768

Effect of natalizumab treatment on soluble adhesion molecules

K Oppermann 1, G Pilz 1, P Wipfler 1, C Sulzer 1, S Afazel 1, E Haschke-Becher 1, A Kunz 1, S Golaszewski 1, G Ladurner 1, J Kraus 1
  • 1Salzburg, A

Introduction: Natalizumab (Tysabri) is a monoclonal antibody used in the treatment of multiple sclerosis (MS). This humanized antibody binds directly at the α4-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 three months after onset of Natalizumab treatment.

Methods: We determined serum concentration levels of 4 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 three 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: 100ng/ml; after three months: 61ng/ml; p<0,001) and sVCAM-1 (before therapy: 580ng/ml; after three months: 216ng/ml; p<0,001) levels three months after onset of Natalizumab treatment. In contrast, serum levels of soluble ICAM-1 (before therapy: 452ng/ml; after three months: 479ng/ml) and ICAM-2 (before therapy: 263U/ml; after three months: 242U/ml) remained unchanged.

Conclusion: We were able to show a differenzial effect after three 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