Contributions
Abstract: P853
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Serum neurofilament light chains (sNfL) have emerged as a promising biomarker of neurodegeneration in multiple sclerosis (MS). Our MS Twin Study of monozygotic, MS-discordant twins offers particular advantages for further evaluating the role of this new biomarker: (1) the twin study design compensates for genetic influences as well as various other confounders by comparing pairs of genetically identical subjects who are discordant for MS; (2) since healthy monozygotic co-twins have the highest possible genetic risk for developing MS, with an estimated concordance rate of around 25%, longitudinal samplingcan be used to validate NfL as a marker for identification of early subclinical disease and potentially prognostic risk marker for conversion of prodromal stages to clinically definite MS.
Objectives: Our MS-discordant Twin cohort provides an excellent opportunity for validating NfL as disease-associated biomarker in genetically identical twins. Furthermore, it allows us to explore the potential role of NfL as a predictive biomarker in healthy co-twins who are at a very high genetic risk of developing MS.
Methods: NfL concentrations were analysed with a sensitive single molecule array (Simoa) in cross-sectional (n= 54 twin pairs) serum samples from the MS Twin cohort. NfL values were classified as increased (according to Disanto et al., 2017) if above the 80th age-corrected percentile.
Within-pair sNfL differences were tested using the Wilcoxon signed-rank test and correlations are expressed as Pearson's correlation coefficient (r). In addition, NfL concentrations in CSF samples from selected twins (n=22, thereof 17 healthy co-twins (HT), 5 MS-affected co-twins (MST)) were analysed.
Results: CSF-NfL levels correlated highly with sNfL levels (r=0.78, p=0.0001). sNfL values were significantly lower in HT than in MST (n=54, median = 20.0 pg/ml, interquartile range (IQR) = 15.5-28.2 versus median = 25.7 pg/ml, IQR = 18.1-41.5, p < 0.0001). sNfL levels values were increased in 13/54 HT, thereof 4/13 (all >95th) presented with signs of subclinical neuroinflammation in CSF and/or MRI assessment, 5/13 displayed vascular MRI lesions (CSF tested in 3/5 with normal results), 1/13 presented with cerebellar atrophy and in 3/13 MRI was normal.
Conclusion: Assessment of sNfL and CSF-NfL values in genetically identical twins discordant for MS identified the clinical MS disease status as well as subclinical neuroinflammation.
Disclosure: Source of funding: The study was funded by the Gemeinnützige Hertie Foundation. The National Twin cohort receives financial support for travel expenses of the twins (for study visits in Munich) by the German MS Foundation, regional and national division (DMSG Landesverband und Bundesverband Bayern) and the association “Therapieforschung für Multiple Sklerose Kranke”.
Disclosures: Lisa A. Gerdes has received speaker´s honoraria from Roche, Sanofi Genzyme and Merck Serono.
Nicole Y.P. Souren:nothing to disclose.
Christian Barro received travel support by Teva and Novartis.
Zuzanna Michalak: nothing to disclose
Andrea Flierl-Hecht: nothing to disclose.
Ludwig KapposInstitution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundation
T. Kümpfel has received travel expenses and speaker honoraria from Bayer Healthcare, Teva Pharma, Merck, Novartis Pharma, Sanofi-Aventis/Genzyme, CLB Behring, Roche Pharma and Biogen as well as grant support from Bayer-Schering AG, Novartis and Chugai Pharma.
Birgit Ertl-Wagner has received speaker honoraria and travel expenses from Novartis Pharma and Bracco.
Frederik Barkhof acts as a consultant to Biogen-Idec, Janssen Alzheimer Immunotherapy, Bayer-Schering, Merck-Serono, Roche, Novartis, Genzyme, and Sanofi-aventis. He has received sponsorship from EU-H2020, NWO, SMSR, EU-FP7, TEVA, Novartis, and Toshiba.
Reinhard Hohlfeldreceived research grants and/or speaker honoraria from Actelion, Genzyme-Sanofi, Novartis, Immunic, Roche.
Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.
Abstract: P853
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Serum neurofilament light chains (sNfL) have emerged as a promising biomarker of neurodegeneration in multiple sclerosis (MS). Our MS Twin Study of monozygotic, MS-discordant twins offers particular advantages for further evaluating the role of this new biomarker: (1) the twin study design compensates for genetic influences as well as various other confounders by comparing pairs of genetically identical subjects who are discordant for MS; (2) since healthy monozygotic co-twins have the highest possible genetic risk for developing MS, with an estimated concordance rate of around 25%, longitudinal samplingcan be used to validate NfL as a marker for identification of early subclinical disease and potentially prognostic risk marker for conversion of prodromal stages to clinically definite MS.
Objectives: Our MS-discordant Twin cohort provides an excellent opportunity for validating NfL as disease-associated biomarker in genetically identical twins. Furthermore, it allows us to explore the potential role of NfL as a predictive biomarker in healthy co-twins who are at a very high genetic risk of developing MS.
Methods: NfL concentrations were analysed with a sensitive single molecule array (Simoa) in cross-sectional (n= 54 twin pairs) serum samples from the MS Twin cohort. NfL values were classified as increased (according to Disanto et al., 2017) if above the 80th age-corrected percentile.
Within-pair sNfL differences were tested using the Wilcoxon signed-rank test and correlations are expressed as Pearson's correlation coefficient (r). In addition, NfL concentrations in CSF samples from selected twins (n=22, thereof 17 healthy co-twins (HT), 5 MS-affected co-twins (MST)) were analysed.
Results: CSF-NfL levels correlated highly with sNfL levels (r=0.78, p=0.0001). sNfL values were significantly lower in HT than in MST (n=54, median = 20.0 pg/ml, interquartile range (IQR) = 15.5-28.2 versus median = 25.7 pg/ml, IQR = 18.1-41.5, p < 0.0001). sNfL levels values were increased in 13/54 HT, thereof 4/13 (all >95th) presented with signs of subclinical neuroinflammation in CSF and/or MRI assessment, 5/13 displayed vascular MRI lesions (CSF tested in 3/5 with normal results), 1/13 presented with cerebellar atrophy and in 3/13 MRI was normal.
Conclusion: Assessment of sNfL and CSF-NfL values in genetically identical twins discordant for MS identified the clinical MS disease status as well as subclinical neuroinflammation.
Disclosure: Source of funding: The study was funded by the Gemeinnützige Hertie Foundation. The National Twin cohort receives financial support for travel expenses of the twins (for study visits in Munich) by the German MS Foundation, regional and national division (DMSG Landesverband und Bundesverband Bayern) and the association “Therapieforschung für Multiple Sklerose Kranke”.
Disclosures: Lisa A. Gerdes has received speaker´s honoraria from Roche, Sanofi Genzyme and Merck Serono.
Nicole Y.P. Souren:nothing to disclose.
Christian Barro received travel support by Teva and Novartis.
Zuzanna Michalak: nothing to disclose
Andrea Flierl-Hecht: nothing to disclose.
Ludwig KapposInstitution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundation
T. Kümpfel has received travel expenses and speaker honoraria from Bayer Healthcare, Teva Pharma, Merck, Novartis Pharma, Sanofi-Aventis/Genzyme, CLB Behring, Roche Pharma and Biogen as well as grant support from Bayer-Schering AG, Novartis and Chugai Pharma.
Birgit Ertl-Wagner has received speaker honoraria and travel expenses from Novartis Pharma and Bracco.
Frederik Barkhof acts as a consultant to Biogen-Idec, Janssen Alzheimer Immunotherapy, Bayer-Schering, Merck-Serono, Roche, Novartis, Genzyme, and Sanofi-aventis. He has received sponsorship from EU-H2020, NWO, SMSR, EU-FP7, TEVA, Novartis, and Toshiba.
Reinhard Hohlfeldreceived research grants and/or speaker honoraria from Actelion, Genzyme-Sanofi, Novartis, Immunic, Roche.
Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.