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4 Differential down-regulation of soluble adhesion molecules during Natalizumab treatment

Published online by Cambridge University Press:  24 June 2014

J. Kraus,
K. Oppermann,
G. Pilz,
P. Wipfler,
C. Sulzer,
S. Afazel,
E. Haschke-Becher,
A. Kunz,
S. Golaszewski and
G. Ladurner
J. Kraus
Affiliation:
University Hospital of Neurology, Paracelsus Medical University and Salzburger Landesklinken, Christian-Doppler-Klinik, Ignaz-Harrer-Str. 79, 5020 Salzburg, Austria, E-mail: joerg.kraus@salk.at
K. Oppermann
Affiliation:
University Hospital of Neurology, Paracelsus Medical University and Salzburger Landesklinken, Christian-Doppler-Klinik, Ignaz-Harrer-Str. 79, 5020 Salzburg, Austria, E-mail: joerg.kraus@salk.at
G. Pilz
Affiliation:
University Hospital of Neurology, Paracelsus Medical University and Salzburger Landesklinken, Christian-Doppler-Klinik, Ignaz-Harrer-Str. 79, 5020 Salzburg, Austria, E-mail: joerg.kraus@salk.at
P. Wipfler
Affiliation:
University Hospital of Neurology, Paracelsus Medical University and Salzburger Landesklinken, Christian-Doppler-Klinik, Ignaz-Harrer-Str. 79, 5020 Salzburg, Austria, E-mail: joerg.kraus@salk.at
C. Sulzer
Affiliation:
University Hospital of Neurology, Paracelsus Medical University and Salzburger Landesklinken, Christian-Doppler-Klinik, Ignaz-Harrer-Str. 79, 5020 Salzburg, Austria, E-mail: joerg.kraus@salk.at
S. Afazel
Affiliation:
University Hospital of Neurology, Paracelsus Medical University and Salzburger Landesklinken, Christian-Doppler-Klinik, Ignaz-Harrer-Str. 79, 5020 Salzburg, Austria, E-mail: joerg.kraus@salk.at
E. Haschke-Becher
Affiliation:
University Hospital of Neurology, Paracelsus Medical University and Salzburger Landesklinken, Christian-Doppler-Klinik, Ignaz-Harrer-Str. 79, 5020 Salzburg, Austria, E-mail: joerg.kraus@salk.at
A. Kunz
Affiliation:
University Hospital of Neurology, Paracelsus Medical University and Salzburger Landesklinken, Christian-Doppler-Klinik, Ignaz-Harrer-Str. 79, 5020 Salzburg, Austria, E-mail: joerg.kraus@salk.at
S. Golaszewski
Affiliation:
University Hospital of Neurology, Paracelsus Medical University and Salzburger Landesklinken, Christian-Doppler-Klinik, Ignaz-Harrer-Str. 79, 5020 Salzburg, Austria, E-mail: joerg.kraus@salk.at
G. Ladurner
Affiliation:
University Hospital of Neurology, Paracelsus Medical University and Salzburger Landesklinken, Christian-Doppler-Klinik, Ignaz-Harrer-Str. 79, 5020 Salzburg, Austria, E-mail: joerg.kraus@salk.at
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Abstract

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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