RT Journal Article
SR Electronic
T1 EFFECT OF TYSABRI AND AQP4-IGG ON AN IN-VITRO MODEL OF BBB
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP e4
OP e4
DO 10.1136/jnnp-2014-309236.162
VO 85
IS 10
A1 McQuaid, Conor
A1 Jacob, Anu
A1 Patabendige, Adjanie
YR 2014
UL http://jnnp.bmj.com/content/85/10/e4.71.abstract
AB Background Neuromyelitis Optica (NMO) is an inflammatory, astrocytopathic, demyelinating disease of the CNS mediated by anti AQP4-IgG that targets the AQP4 protein, the dominant water channel on astrocyte foot processes at the blood brain barrier (BBB). Natalizimumab (NTZ, Tysabri) prevents migration of activated T lymphocytes across the BBB and is effective in preventing inflammation in MS. However, for unknown reasons, NTZ worsens NMO, precipitating relapses. We explored the effect of NTZ on a model of BBB.Methods Using an in-vitro culture model of BBB (Human Brain Endothelial Cells (HBEC) and Human Astrocytes) tightness of HBEC layer was measured using Trans-Endothelial Electrical Resistance (TEER).Results Addition of NTZ to the model caused TEER values to reduce significantly compared to control. Addition of AQP4-IgG and NTZ caused further significant reduction of TEER. Addition of just the AQP4-IgG did not have any effect.Conclusion NTZ apparently lowers surrogate measures of BBB integrity in the presence of AQP4-IgG. Whether this in vitro effect translates to easier access of AQP4-IgG to the AQP4 in-vivo or predisposes to attacks is uncertain and is being explored.