Contributions
Abstract: P728
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Interferon-beta (IFN-beta) is an established first-line therapy in multiple sclerosis (MS). Previous studies have identified more than a hundred genes to be differentially expressed in response to this treatment. Most of these studies used mixed cell populations such as whole blood or peripheral blood mononuclear cells (PBMC), in which cell type-specific effects may be masked. We compared the gene expression profiles of 5 immune cell populations before and during treatment with subcutaneous IFN-beta to obtain deeper insights into the drug´s mechanisms of action and to confirm and refine potential biomarkers for therapy monitoring and disease prognosis.
With written informed consent, blood samples were collected from 32 patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) before as well as 2 days and 1 month after the start of IFN-beta therapy. T helper cells (CD4+), cytotoxic T-cells (CD8+), monocytes (CD14+), B-cells (CD19+) and PBMC were separated by Ficoll gradient and magnetic-activated cell sorting. The OpenArray real-time PCR platform was used for sensitive high-throughput quantification of 112 transcripts. Expression differences with t-test p-value < 0.05 and log2 fold-change >0.5 or < -0.5 were considered statistically significant.
About 42300 real-time PCR reactions were evaluated. The data showed that the IFN-beta signature is induced in particular in monocytes. Approximately half of the IFN-beta-responsive genes seen after 1 month were significantly changed in expression already after the first injection. IFI44, MX1 and XAF1 were consistently expressed at higher mRNA levels in all 5 cell populations and at both time points during therapy. Differences in baseline expression of genes belonging to the JAK/STAT pathway distinguished patients with and without relapses in the clinical follow-up.
The treatment with subcutaneous IFN-beta evoked different gene regulatory effects in different cell types of the blood. IFN-beta-responsive genes were typically increased in expression in monocytes after 1 month of therapy. Cell type-specific gene expression differences prior to therapy may be useful as biomarkers of the biological and clinical response to therapy.
Disclosure:
MH received speaking fees and travel support from Bayer, Biogen, Novartis and Teva.
BF declares no conflicts of interest.
DK declares no conflicts of interest.
IS declares no conflicts of interest.
HJT declares no conflicts of interest.
UKZ received speaking fees and financial support for research activities from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Almirall and Teva.
Abstract: P728
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Interferon-beta (IFN-beta) is an established first-line therapy in multiple sclerosis (MS). Previous studies have identified more than a hundred genes to be differentially expressed in response to this treatment. Most of these studies used mixed cell populations such as whole blood or peripheral blood mononuclear cells (PBMC), in which cell type-specific effects may be masked. We compared the gene expression profiles of 5 immune cell populations before and during treatment with subcutaneous IFN-beta to obtain deeper insights into the drug´s mechanisms of action and to confirm and refine potential biomarkers for therapy monitoring and disease prognosis.
With written informed consent, blood samples were collected from 32 patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) before as well as 2 days and 1 month after the start of IFN-beta therapy. T helper cells (CD4+), cytotoxic T-cells (CD8+), monocytes (CD14+), B-cells (CD19+) and PBMC were separated by Ficoll gradient and magnetic-activated cell sorting. The OpenArray real-time PCR platform was used for sensitive high-throughput quantification of 112 transcripts. Expression differences with t-test p-value < 0.05 and log2 fold-change >0.5 or < -0.5 were considered statistically significant.
About 42300 real-time PCR reactions were evaluated. The data showed that the IFN-beta signature is induced in particular in monocytes. Approximately half of the IFN-beta-responsive genes seen after 1 month were significantly changed in expression already after the first injection. IFI44, MX1 and XAF1 were consistently expressed at higher mRNA levels in all 5 cell populations and at both time points during therapy. Differences in baseline expression of genes belonging to the JAK/STAT pathway distinguished patients with and without relapses in the clinical follow-up.
The treatment with subcutaneous IFN-beta evoked different gene regulatory effects in different cell types of the blood. IFN-beta-responsive genes were typically increased in expression in monocytes after 1 month of therapy. Cell type-specific gene expression differences prior to therapy may be useful as biomarkers of the biological and clinical response to therapy.
Disclosure:
MH received speaking fees and travel support from Bayer, Biogen, Novartis and Teva.
BF declares no conflicts of interest.
DK declares no conflicts of interest.
IS declares no conflicts of interest.
HJT declares no conflicts of interest.
UKZ received speaking fees and financial support for research activities from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Almirall and Teva.