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Abstract Details

Identification of multiple sclerosis endophenotypes by high dimensional blood signatures associated with distinct disease trajectories
Multiple Sclerosis
P1 - Poster Session 1 (8:00 AM-9:00 AM)
3-008
MS is a neuro-immunological disease representing with a broad spectrum of clinical manifestations and disease progression. To date it is still controversially discussed, whether discrete immune-response signatures in the blood represent inflammatory disease characteristics versus signs of early neurodegeneration with prognostic and therapeutic consequences.
To identify immune-response signatures in the blood of multiple sclerosis (MS) patients predictive for clinical disease trajectories and supporting personalized treatment decisions based on pathobiological principles.
In this multicentric prospective study, we employed high-dimensional flow cytometry and targeted proteomics to a discovery cohort of 378 treatment-naïve early (£ 2years from disease onset) MS patients from the NationMS cohort with comprehensive clinical and paraclinical data. Resulting data were analyzed applying state-of-the-art computational biology. Results were reproduced in a validation cohort of 78 MS patients.
We identified MS as a disease of disturbed immune-regulatory networks that can be detected in the blood. Early MS consists of four immunological endophenotypes associated with different HLA-backgrounds suggestive for discrete immunological pathways in disease pathogenesis. Immunological endophenotypes were mirrored by specific clinical and paraclinical disease trajectories exhibiting inflammatory disease characteristics versus signs of early neurodegeneration. Distinct immune-therapeutic principles differed in their capacity to normalize immune-response signatures associated with each endophenotype, exemplified by the limited effect of interferon-beta on immune-response signatures in patients with the inflammatory endophenotype, which was accompanied by increased clinical and imaging features of diseases progression in these patients.
Ascertaining immune-response signatures in the blood of MS patients is an innovative clinical tool for predicting longitudinal outcomes and guiding personalized treatment decisions based on pathobiological principles.
Authors/Disclosures
Luisa Hildegard Klotz, MD (Uniklinik Münster)
PRESENTER
Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Dr. Klotz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Klotz has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genzyme. Dr. Klotz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Klotz has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck Serono. Dr. Klotz has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Klotz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Klotz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viatris. Dr. Klotz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. The institution of Dr. Klotz has received research support from Immunic AG. The institution of Dr. Klotz has received research support from Merck.
Catharina Groß The institution of Catharina Groß has received research support from Biogen. The institution of Catharina Groß has received research support from Roche.
Andreas Schulte-Mecklenbeck Andreas Schulte-Mecklenbeck has nothing to disclose.
Olga Vsevolodivna Steinberg Mrs. Steinberg has nothing to disclose.
Timo Wirth Timo Wirth has nothing to disclose.
Sarah Lauks, MD (Uniklinik Münster) Dr. Lauks has nothing to disclose.
Sergio Baranzini (UCSF) Sergio Baranzini has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Serono. Sergio Baranzini has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Sergio Baranzini has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Aventis. Sergio Baranzini has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nexilico. Sergio Baranzini has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono . Sergio Baranzini has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD SErono. Sergio Baranzini has stock in MATE Bioservices. The institution of Sergio Baranzini has received research support from Valhalla Charitable Fund. The institution of Sergio Baranzini has received research support from Genentech Inc. The institution of Sergio Baranzini has received research support from Salah Foundation.
Stefan Bittner Stefan Bittner has received personal compensation in the range of $500-$4,999 for serving as a Honoria with Biogen Idec. Stefan Bittner has received personal compensation in the range of $500-$4,999 for serving as a Honoria with Merck Healthcare. Stefan Bittner has received personal compensation in the range of $500-$4,999 for serving as a Honoria with Novartis. Stefan Bittner has received personal compensation in the range of $500-$4,999 for serving as a Honoria with Roche. Stefan Bittner has received personal compensation in the range of $500-$4,999 for serving as a Honoria with Sanofi. Stefan Bittner has received personal compensation in the range of $500-$4,999 for serving as a Honoria with Bristol-Meyer-Squibbs. Stefan Bittner has received personal compensation in the range of $500-$4,999 for serving as a Honoria with Teva.
Judith Bellmann-Strobl, MD (Bharite University of Medicine Berlin) Judith Bellmann-Strobl, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Judith Bellmann-Strobl, MD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Judith Bellmann-Strobl, MD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Judith Bellmann-Strobl, MD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Judith Bellmann-Strobl, MD has received research support from Bayer. The institution of Judith Bellmann-Strobl, MD has received research support from NEMOS.
Nora Buenger, MD (University Clinics Muenster) Dr. Buenger has nothing to disclose.
Eva Eilers, PhD Dr. Eilers has nothing to disclose.
Maria Eveslage Maria Eveslage has nothing to disclose.
Vinzenz Fleischer, MD Dr. Fleischer has nothing to disclose.
Barbara Gisevius, PhD (Ruhr-University Bochum) Dr. Gisevius has nothing to disclose.
Sergiu Groppa Sergiu Groppa has nothing to disclose.
Juergen Haas Juergen Haas has nothing to disclose.
Martin Kerschensteiner, MD Prof. Kerschensteiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Prof. Kerschensteiner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Aventis. Prof. Kerschensteiner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Healtcare. Prof. Kerschensteiner has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Prof. Kerschensteiner has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck Healthcare. Prof. Kerschensteiner has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi-Aventis. Prof. Kerschensteiner has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva.
Lucienne Kirstein, MD Dr. Kirstein has nothing to disclose.
Catharina Korsukewitz, MD Dr. Korsukewitz has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Merck. Dr. Korsukewitz has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Korsukewitz has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen.
Lisa Lohmann Lisa Lohmann has nothing to disclose.
Jan Lünemann, MD (University and University Hospital of Münster) Dr. Lünemann has received personal compensation in the range of $0-$499 for serving as a Consultant for Takeda. Dr. Lünemann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Lünemann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck & Co. Dr. Lünemann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AbbVie. Dr. Lünemann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Lünemann has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ArgenX. Dr. Lünemann has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Lünemann has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Lünemann has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for CSL Behring. Dr. Lünemann has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Lünemann has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB Biopharma GmbH. The institution of Dr. Lünemann has received research support from German Research Foundation. The institution of Dr. Lünemann has received research support from French National Research Agency (ANR). The institution of Dr. Lünemann has received research support from National Multiple Sclerosis Society (NMSS). The institution of Dr. Lünemann has received research support from National Institute of Health.
Felix Lüssi, MD Dr. Lüssi has nothing to disclose.
Gerd Meyer Zu Horste, MD (University Hospital Muenster) Dr. Meyer Zu Horste has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for LFB. The institution of Dr. Meyer Zu Horste has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Meyer Zu Horste has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. The institution of Dr. Meyer Zu Horste has received research support from Merck KGaA. The institution of Dr. Meyer Zu Horste has received research support from Roche. Dr. Meyer Zu Horste has received intellectual property interests from a discovery or technology relating to health care.
Jeremias Motte, MD (UK RUB- St. Josef-Hospital) The institution of Dr. Motte has received research support from Ruhr-Univerity Bochum.
Tobias Ruck, MD (Heinrich-Heine-University Düsseldorf, Department of Neurology) Dr. Ruck has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme.
Nicholas Schwab The institution of Nicholas Schwab has received research support from Biogen. The institution of Nicholas Schwab has received research support from Roche.
Sven G. Meuth (Uniklinik Düsseldorf, Klinik für Neurologie) Sven G. Meuth has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck. Sven G. Meuth has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Sven G. Meuth has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Almirall. Sven G. Meuth has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Sven G. Meuth has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Sven G. Meuth has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Sven G. Meuth has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TEVA. Sven G. Meuth has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche.
Friedemann Paul (Charite Universitatsmedizin in Berlin) The institution of Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe PC (MTPC). The institution of Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aarhus University. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Paul has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CELGENE. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACRELION. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Viela Bio. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pfizter. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck Serono. The institution of Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer.
Brigitte Wildemann, MD (University Hospital Heidelberg, Department of Neurology) Dr. Wildemann has nothing to disclose.
Tania Kuempfel, MD (Institut for Klinische Neuroimmunologie) Dr. Kuempfel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Pharma. Dr. Kuempfel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BIOGEN. Dr. Kuempfel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Kuempfel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Kuempfel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Kuempfel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Kuempfel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion.
Ralf Gold, MD (Neurologische Universitaetsklinik) Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen . Dr. Gold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer Vital. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Pharamaceuticals. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for SAGE Publishers. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Novartis. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Biogen. The institution of Dr. Gold has received research support from Novartis. The institution of Dr. Gold has received research support from Biogen.
Frauke Zipp, MD (University Medical Center Mainz) Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Dr. Zipp has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Octapharma. Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TEVA. The institution of Dr. Zipp has received research support from BMBF. The institution of Dr. Zipp has received research support from DFG. The institution of Dr. Zipp has received research support from PMSA. The institution of Dr. Zipp has received research support from Sanofi Genzyme. The institution of Dr. Zipp has received research support from UCB. The institution of Dr. Zipp has received research support from Eisai. The institution of Dr. Zipp has received research support from SK Life Science. The institution of Dr. Zipp has received research support from Abbott. The institution of Dr. Zipp has received research support from Actelion. The institution of Dr. Zipp has received research support from Bayer. The institution of Dr. Zipp has received research support from Servier. Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving as a Reviewer with Novartis. Dr. Zipp has received personal compensation in the range of $0-$499 for serving as a Reviewer with Universite de Geneve. Dr. Zipp has received personal compensation in the range of $5,000-$9,999 for serving as a Reviewer with Oppenheim Förderpreis für Multiple Sklerose. Dr. Zipp has received personal compensation in the range of $500-$4,999 for serving as a Reviewer with EKFS. Dr. Zipp has a non-compensated relationship as a Associate Editor with Brain that is relevant to AAN interests or activities. Dr. Zipp has a non-compensated relationship as a Advisor with Science Translational Medicine that is relevant to AAN interests or activities.
Heinz Wiendl, MD, FAAN (University of Muenster) Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Johnson&Johnson / Janssen. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Wiendl has received personal compensation in the range of $0-$499 for serving as a Consultant for Idorsia. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Immunic. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NexGen. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Worldwide Clinical Trials. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BD. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gossamer Bio. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for LTS. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Samsung. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sangamo. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz-Hexal. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cellerys. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dianthus. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Toleranzia. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Uniqure. The institution of Dr. Wiendl has received research support from Biogen. The institution of Dr. Wiendl has received research support from Roche. The institution of Dr. Wiendl has received research support from Deutsche Forschungsgemeinschaft. The institution of Dr. Wiendl has received research support from European Union. The institution of Dr. Wiendl has received research support from Argenx. The institution of Dr. Wiendl has received research support from CSL Behring. The institution of Dr. Wiendl has received research support from Merck. The institution of Dr. Wiendl has received research support from UCB. Dr. Wiendl has received publishing royalties from a publication relating to health care. Dr. Wiendl has received publishing royalties from a publication relating to health care.