Change in lymphocyte gene expression induced by Campath-1H treatment of multiple sclerosis
J.A. Somerfield, J.L. Jones, V.H. Robertson, D.A.S. Compston, A.J. Coles (Cambridge, UK)
Objectives: Campath-1H, a humanised monoclonal antibody to CD52, causes profound lymphopenia. It significantly reduces the relapse rate of multiple sclerosis and, intriguingly, results in reduced EDSS scores at 36months. This study aims to identify changes in peripheral lymphocyte gene expression associated with this improvement in disability after Campath-1H treatment.
Methods: Blood was obtained from patients with early, aggressive, RRMS participating in one of two clinical trials of Campath-1H treatment: CAMMS-223 and CAMMS-224. CD4+ peripheral blood mononuclear cells were isolated and total RNA extracted. An Affymetrix microarray was performed and genes were identified that were increased or decreased by a factor of greater than 1.5. RNA was then reverse transcribed to cDNA and quantitative real-time polymerase chain reaction (PCR) was performed.
Results: The Affymetrix microarray on four patients identified 42 up-regulated genes and 8 down-regulated genes. 16 of these genes with a role in neuronal repair were validated by real-time PCR on a total of 8 patients and 5 healthy controls.
Conclusion: Analysis of RNA from lymphocytes of patients with RRMS treated with Campath-1H show an up and down-regulation of genes that contribute to neuronal repair.
I have been waiting on this to be published, but I guess I missed it. I would buy the whole article if I knew it provided some info on how these genes could be controlled, that is without the Campath dose.
