Analysis of the Effect On the Expression of Global Gene Expression Profiles in Lymphocyte Subpopulations Treated by Extracorporeal Photopheresis

After the initial introduction of extracorporeal photopheresis (ECP) for the therapy of Sezary syndrome (CTCL) it has been found to have significant clinical effect on other T-cell mediated diseases including graft-versus-host disease (GvHD), organ transplant rejection, systemic sclerosis and other autoimmune disorders.

To obtain information about modifications in gene expression patterns before and after ECP and to define gene sets with important changes in expression we analysed gene expression profiles in major lymphocyte subsets of patients before and after treatment with 8-methoxypsoralen (8-MOP) and ultraviolet A (UVA) irradiation.

For this initial study 6 female patients suffering from chronic GvHD under treatment with ECP were included. Affymetrix® Human Genome U133 Plus 2.0 Arrays were used to compare global gene expression profiles in CD4+ and CD8+ lymphocytes before and after ECP. Lymphocyte subsets were isolated before and immediately after exposure to 8-MOP/UVA during a standard ECP treatment cycle. Total RNA was isolated from each cell sample and processed and analyzed according to standard procedures.

Preliminary data suggest a significant effect in CD4+ and CD8+ lymphocytes in patients with chronic GvHD on gene transcription after 8-MOP/UVA exposure. In CD4+ cells 20 times more gene transcription can be detected when compared to CD8+ cells.

These findings underline the possible key role of CD4+ cells in the mechanisms of action of ECP. Recent research in animal models found evidence for a role of CD4+ regulatory T cells in the immunomodulatory activity of ECP.

The scientific approach of this study has the advantage of exploring global gene regulatory effects of ECP without any experimental bias based on earlier evidence or on a mechanistic hypothesis. Its results offer the advantage of finding new and so far unexplored effects of ECP on the treated cells; information which should be able to generate significant data to help define key targets for subsequent research into the mechanism of action of ECP.

No relevant conflicts of interest to declare.