Contributions
Abstract: P639
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Genetic variants within some cytokine receptor genes have been associated with multiple sclerosis (MS) susceptibility, including interleukin 7 receptor (IL7RA) and interleukin 2 receptor alpha (IL2RA). As these genes are expressed by cells targeted by immune-modulatory drugs, we explored the potential role of their gene products as biomarkers in monitoring MS treatment. Here we specifically assessed the impact of natalizumab and fingolimod on the intra-individual changes of soluble protein levels of sIL-7Rα and sIL-2Rα. In addition, we included protein levels of soluble interleukin-6 receptor (sIL-6R) and the soluble glycoprotein 130 (sgp130) in the study. Analysis of serial plasma samples from patients during natalizumab and subsequent fingolimod treatment revealed a decline in the plasma levels of sgp130 and sIL-7Rα during natalizumab treatment (P= 0.009 and 0.006, respectively). During fingolimod treatment the plasma levels of sIL-2Rα declined while sgp130 and sIL-7Rα increased (P= 6x10-11, 2.2x10-5 and 8x10-5, respectively). We replicated the previous observation that patients with the MS associated genotype of rs6897932 in the IL7RA gene have higher plasma levels of sIL-7Rα. Furthermore, the plasma levels of sIL-7Rα during fingolimod treatment were increasing significantly more in patients homozygous for the MS risk genotype than in patients from the other genotype groups (P=0.0007). In addition, we observed a protein quantitative trait locus effect of the MS associated SNP rs71624119 on the levels of sgp130. Monitoring the changes in the plasma levels of these soluble cytokine receptors in a well-defined cohort of MS patients during treatments will determine the possibility of using these proteins as biomarkers for treatment response. By exploring the MS associated risk variants in the context of clinical information one may elucidate the pharmacodynamics of treatments with the eventual aim to identify biomarkers for MS outcomes.
Disclosure:
Sahl Khalid Bedri: nothing to disclose.
Ali Manouchehrinia: nothing to disclose.
Wangko Lundström: nothing to disclose.
Katharina Fink: has received an unrestricted research grant from Biogen, Neuroförbundet and MS forskningsfonden and travel compensations for holding lectures by Biogen, Teva, Roche and Novartis.
Ingrid Kockum: has received travel compensation for holding lectures by Merck Serono. Tomas Olsson received compensation for serving on scientific advisory boards or conducting lectures for Biogen and Genzyme, as well as unrestricted research grants from Biogen, Novartis, Genzyme, Almirall, and AstraZeneca.
Jan Hillert: received honoraria for serving on advisory boards for Biogen and Novartis and speaker's fees from Biogen, Merck Serono, Bayer Schering, Teva and Sanofi Genzyme. He has served as P.I. for projects sponsored by, or received unrestricted research support from, Biogen, Sanofi Genzyme, Merck Serono, TEVA, Novartis and Bayer Schering. His MS research is funded by the Swedish Research Council and the Swedish Brain Foundation.
Anna Glaser has received unrestricted research support from Biogen.
Abstract: P639
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Genetic variants within some cytokine receptor genes have been associated with multiple sclerosis (MS) susceptibility, including interleukin 7 receptor (IL7RA) and interleukin 2 receptor alpha (IL2RA). As these genes are expressed by cells targeted by immune-modulatory drugs, we explored the potential role of their gene products as biomarkers in monitoring MS treatment. Here we specifically assessed the impact of natalizumab and fingolimod on the intra-individual changes of soluble protein levels of sIL-7Rα and sIL-2Rα. In addition, we included protein levels of soluble interleukin-6 receptor (sIL-6R) and the soluble glycoprotein 130 (sgp130) in the study. Analysis of serial plasma samples from patients during natalizumab and subsequent fingolimod treatment revealed a decline in the plasma levels of sgp130 and sIL-7Rα during natalizumab treatment (P= 0.009 and 0.006, respectively). During fingolimod treatment the plasma levels of sIL-2Rα declined while sgp130 and sIL-7Rα increased (P= 6x10-11, 2.2x10-5 and 8x10-5, respectively). We replicated the previous observation that patients with the MS associated genotype of rs6897932 in the IL7RA gene have higher plasma levels of sIL-7Rα. Furthermore, the plasma levels of sIL-7Rα during fingolimod treatment were increasing significantly more in patients homozygous for the MS risk genotype than in patients from the other genotype groups (P=0.0007). In addition, we observed a protein quantitative trait locus effect of the MS associated SNP rs71624119 on the levels of sgp130. Monitoring the changes in the plasma levels of these soluble cytokine receptors in a well-defined cohort of MS patients during treatments will determine the possibility of using these proteins as biomarkers for treatment response. By exploring the MS associated risk variants in the context of clinical information one may elucidate the pharmacodynamics of treatments with the eventual aim to identify biomarkers for MS outcomes.
Disclosure:
Sahl Khalid Bedri: nothing to disclose.
Ali Manouchehrinia: nothing to disclose.
Wangko Lundström: nothing to disclose.
Katharina Fink: has received an unrestricted research grant from Biogen, Neuroförbundet and MS forskningsfonden and travel compensations for holding lectures by Biogen, Teva, Roche and Novartis.
Ingrid Kockum: has received travel compensation for holding lectures by Merck Serono. Tomas Olsson received compensation for serving on scientific advisory boards or conducting lectures for Biogen and Genzyme, as well as unrestricted research grants from Biogen, Novartis, Genzyme, Almirall, and AstraZeneca.
Jan Hillert: received honoraria for serving on advisory boards for Biogen and Novartis and speaker's fees from Biogen, Merck Serono, Bayer Schering, Teva and Sanofi Genzyme. He has served as P.I. for projects sponsored by, or received unrestricted research support from, Biogen, Sanofi Genzyme, Merck Serono, TEVA, Novartis and Bayer Schering. His MS research is funded by the Swedish Research Council and the Swedish Brain Foundation.
Anna Glaser has received unrestricted research support from Biogen.