bartman wrote:Having just been on Tysarbri, you have basically wiped out your immune system.
This is not correct. Tysabri does not "wipe out" the immune system. It is an antibody which blocks cell adhesion molecules, such as VCAM-1, necessary for T-lymphocytes to cross the blood brain barrier (BBB). The immune system remains active. Indeed, patients coming off of Tysabri often experience Immune Reconstitution Inflammatory Syndrome (IRIS) where the active immune system is now free to cross the BBB and cause enhanced inflammation.
For more details, the following information is quoted from Tysabri's prescribing information. http://www.tysabri.com/en_US/tysb/site/ ... BRI-pi.pdf
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Natalizumab binds to the alpha 4-subunit of alpha 4 beta 1 and alpha 4 beta 7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the alpha 4-mediated adhesion of leukocytes to their counter-receptor(s). The receptors for the alpha 4 family of integrins include vascular cell adhesion molecule-1 (VCAM-1), which is expressed on activated vascular endothelium, and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) present on vascular endothelial cells of the gastrointestinal tract. Disruption of these molecular interactions prevents transmigration of leukocytes across the endothelium into inflamed parenchymal tissue. In vitro, anti-alpha 4-integrin antibodies also block alpha 4- mediated cell binding to ligands such as osteopontin and an alternatively spliced domain of fibronectin, connecting segment-1 (CS-1). In vivo, natalizumab may further act to inhibit the interaction of alpha 4-expressing leukocytes with their ligand(s) in the extracellular matrix and on parenchymal cells, thereby inhibiting further recruitment and inflammatory activity of activated immune cells.
The specific mechanism(s) by which TYSABRI exerts its effects in multiple sclerosis and Crohn’s disease have not been fully defined.
In multiple sclerosis, lesions are believed to occur when activated inflammatory cells, including T-lymphocytes, cross the blood-brain barrier (BBB). Leukocyte migration across the BBB involves interaction between adhesion molecules on inflammatory cells and their counter-receptors present on endothelial cells of the vessel wall. The clinical effect of natalizumab in multiple sclerosis may be secondary to blockade of the molecular interaction of alpha 4 beta 1-integrin expressed by inflammatory cells with VCAM-1 on vascular endothelial cells, and with CS-1 and/or osteopontin expressed by parenchymal cells in the brain. Data from an experimental autoimmune encephalitis animal model of multiple sclerosis demonstrate reduction of leukocyte migration into brain parenchyma and reduction of plaque formation detected by magnetic resonance imaging (MRI) following repeated administration of natalizumab. The clinical significance of these animal data is unknown.