Contributions
Abstract: EP1553
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Nearly all human genes encode multiple transcriptional variants. Previous studies reported genes with altered RNA splicing patterns in multiple sclerosis (MS). We aimed to utilise cell type-specific transcriptome profiles obtained by high-resolution microarrays to further examine the exon composition of these genes in patients with relapsing-remitting MS.
Following the PRISMA guidelines, we screened the literature for studies on splicing in MS, considering only primary research articles with data on human samples. Moreover, we processed a huge dataset comprising 150 Affymetrix HTA 2.0 microarrays to explore the transcriptomes of five different immune cell populations, which were obtained from the peripheral blood of MS patients. Alternative splicing events (ASE) were detected in these data using the EventPointer software.
We identified 38 MS-related publications that investigated alternative RNA variants of in total 28 genes, including IFNAR2, IL7R and MBP. For 21 of those genes, 52 ASE could be retrieved with p-value < 0.01 when we compared the microarray data of the individual MS patients. Most of the ASE were detected in CD56+ natural killer cells. Among the top genes were NFATC1 and NFAT5, two members of the family of nuclear factors of activated T-cells, for which different mRNA isoforms result from usage of an alternative first exon and skipping of a cassette exon, respectively.
To conclude, analyses at exon level can help to achieve a better understanding of transcriptional blood biomarkers for MS. Our study demonstrates that specific transcript variants expressed in immune cell subsets are suited for patient classification. Their predictive value regarding the individual clinical course of the disease remains to be determined.
Disclosure: MH received speaking fees and travel funds from Bayer HealthCare, Biogen, Novartis and Teva. NB received travel funds from Novartis. UKZ received speaking fees and financial support for research activities from Almirall, Bayer HealthCare, Biogen, Merck Serono, Novartis, Sanofi Genzyme and Teva. AR, BF, DK, IS and HJT declare no conflicts of interest. This study was partly funded by Genzyme and Novartis.
Abstract: EP1553
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Nearly all human genes encode multiple transcriptional variants. Previous studies reported genes with altered RNA splicing patterns in multiple sclerosis (MS). We aimed to utilise cell type-specific transcriptome profiles obtained by high-resolution microarrays to further examine the exon composition of these genes in patients with relapsing-remitting MS.
Following the PRISMA guidelines, we screened the literature for studies on splicing in MS, considering only primary research articles with data on human samples. Moreover, we processed a huge dataset comprising 150 Affymetrix HTA 2.0 microarrays to explore the transcriptomes of five different immune cell populations, which were obtained from the peripheral blood of MS patients. Alternative splicing events (ASE) were detected in these data using the EventPointer software.
We identified 38 MS-related publications that investigated alternative RNA variants of in total 28 genes, including IFNAR2, IL7R and MBP. For 21 of those genes, 52 ASE could be retrieved with p-value < 0.01 when we compared the microarray data of the individual MS patients. Most of the ASE were detected in CD56+ natural killer cells. Among the top genes were NFATC1 and NFAT5, two members of the family of nuclear factors of activated T-cells, for which different mRNA isoforms result from usage of an alternative first exon and skipping of a cassette exon, respectively.
To conclude, analyses at exon level can help to achieve a better understanding of transcriptional blood biomarkers for MS. Our study demonstrates that specific transcript variants expressed in immune cell subsets are suited for patient classification. Their predictive value regarding the individual clinical course of the disease remains to be determined.
Disclosure: MH received speaking fees and travel funds from Bayer HealthCare, Biogen, Novartis and Teva. NB received travel funds from Novartis. UKZ received speaking fees and financial support for research activities from Almirall, Bayer HealthCare, Biogen, Merck Serono, Novartis, Sanofi Genzyme and Teva. AR, BF, DK, IS and HJT declare no conflicts of interest. This study was partly funded by Genzyme and Novartis.