Research: Tysabri failure associated with B cell activity in CNS

Villar LM, García-Sánchez MI, Costa-Frossard L, Espiño M, Roldán E, Páramo D, Lucas M, Izquierdo G, Alvarez-Cermeño JC. Immunological markers of optimal response to natalizumab in multiple sclerosis.Arch Neurol. 2012;69:191-7.

To explore cell subsets and molecules that changed specifically in patients with multiple sclerosis (MS) who had an optimal response to natalizumab. Natalizumab is a monoclonal antibody that inhibits the migration of activated immune cells to the central nervous system. It shows high efficacy in modifying the natural history of MS and induces freedom of disease activity in about 40% of treated patients with MS.

DESIGN: Prospective study of intrathecal immunoglobulin synthesis and cerebrospinal fluid lymphocyte subsets in patients with MS before and 1 year after beginning treatment with natalizumab. We monitored clinical and magnetic resonance imaging activity during a median time of 2 years.

RESULTS: Of the 23 patients, 10 (43.5%) remained free of disease activity during follow-up. The remaining 13 patients (56.5%) had relapses or new lesions despite natalizumab therapy. We did not find differences in demographic variables or clinical data between both groups prior to natalizumab therapy. All patients showed a decrease in cerebrospinal fluid CD4(+) cells regardless of their response to treatment. Conversely, only patients free of disease activity showed a decrease in local IgM and, to a lesser extent, in IgG synthesis. They also showed lower percentages of B cells, particularly of CD5(+) and plasmablast subsets that virtually disappeared after treatment with natalizumab.

CONCLUSION: These data indicate that inhibition of intrathecal antibody synthesis is associated with a complete therapeutic response to natalizumab in patients with aggressive MS.

Lumbar puncture, brown stuff is Iodine

This study shows that people who fail tysabri treatment and develop a relapse, have immune activity in the cerebrospinal fluid, whereas those that do not and have immune activity in the brain, notably in the B cell compartment of immune function. Does this mean that it is worth having a lumbar puncture, well probably not because if the drug fails then what is the point in looking in the cerebrospinal fluid as you have relapsed, if you have not relapsed then why have a lumbar puncture. However it points to immune activity as being the cause or at least associated with relapse, so in this case it would look like inflammation is not a good thing