Natalizumab treatment reduces endothelial activity in MS patients.
Vascular cell adhesion molecule-1 a ligand for leukocyte very late activating antigen-4 is a key player in leukocyte extravasation in MS lesions. Natalizumab a monoclonal antibody against VLA-4 blocks this interaction. VCAM-1 and its soluble form are up-regulated during endothelial activation in MS. We investigated the effect of Natalizumab on sVCAM-1 and VLA-4 on circulating leukocytes in MS patients. Natalizumab reduced levels of sVCAM-1 compared to controls (256 vs. 597 ng/mL). This effect was sustained and only reversed in patients with neutralizing antibodies against Natalizumab. Correspondingly Natalizumab diminished VLA-4 on leukocyte subsets. Our findings indicate that Natalizumab reduces transmigration not only by blocking VLA-4 but also by down-regulating VCAM-1.
Millonig
Alban
A
Department of Neurology, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Hegen
Harald
H
Di Pauli
Franziska
F
Ehling
Rainer
R
Gneiss
Claudia
C
Hoelzl
Martina
M
Künz
Bettina
B
Lutterotti
Andreas
A
Rudzki
Dagmar
D
Berger
Thomas
T
Reindl
Markus
M
Deisenhammer
Florian
F
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000097:blood; D002464:Cell Migration Inhibition / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology; D005500:Follow-Up Studies; D006801:Humans; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors / Q000276:immunology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D000069442:Natalizumab; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D039041:Integrin alpha4beta1; D000069442:Natalizumab; D019010:Vascular Cell Adhesion Molecule-1