Contributions
Abstract: P1169
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background and Objectives: To evaluate and validate a subset of candidate biomarkers in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) we prospectively characterized IgG-oligoclonal bands (OCBs), intrathecal IgG antibodies against measles, rubella and varicella zoster viruses (MRZ reaction), CXCL13, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP).
Methods: Patients were recruited from multiple specialized MS centres in Germany. Inclusion criteria were 1) first manifestation of clinically isolated syndrome (CIS) or MS, 2) availability of baseline CSF data, and 3) availability of baseline and follow-up MRI data. CXCL13, NfL and GFAP were measured using classical ELISA, the MRZ reaction was determined by a multiplexing technique. All biomarkers were characterized by comparing their levels to diagnosis, T2 and gadolinium enhanced (GD+) lesions and EDSS at baseline. To evaluate their predictive value, levels were compared to disease progression by clinical or MRI signs and EDSS development within two years.
Results: We collected data from 193 patients with a median age at clinical onset of 31 years (IQR 26-40) and a proportion of females of 75 % (144/193).
At disease onset 91/193 (47%) patients were diagnosed with a CIS and 102/193 (53 %) fulfilled the McDonald 2005 criteria for MS.
OCBs were detectable in 81/91 (89 %) of CIS and 93/102 (91 %) of MS patients and the MRZ reaction in 37/91 (40 %) of CIS and 51/102 (52 %) of MS patients. Only NfL CSF levels were slightly higher in MS compared to CIS patients (p-value= 0.04). CXCL13 and NfL were higher in patients with GD+ lesions compared to patients without GD+ lesion (p-values= 0.092 and 0.011, respectively). Additionally, NfL showed a weak association with EDSS (Spearman rho= 0.18, p-value= 0.015) and with 9 or more T2 lesions compared to 1-8 T2 lesions (p-value< 0.0001). Higher levels of NfL predicted disease progression indicated by MRI within two years (p-value= 0.015) and GFAP levels showed a tendency to be higher if patients had an increase of their EDSS within two years (p-value= 0.05).
Conclusion: Our data show that especially NfL is an informative marker for structural damage, disease severity and progression in MS and CXCL13 may be a marker of disease activity. GFAP is not differentially regulated in the early phase of MS but might be associated with disease progression indicated by EDSS.
Disclosure: A.H.: nothing to disclose.
M.O. reports grants from BMBF (FTLDc), grants from Thierry Latran foundation, grants
from ALS association, grants from Foundation State Baden-Wuerttemberg, grants from Boehringer Ingelheim University Ulm Institute, grants from EU (Fairpark), personal fees from Teva, Fujirebio, personal fees from Axon, Roche, Neuroallianz, outside the submitted work.
B.T.: nothing to disclose.
M.S. has received honoraria for scientific lectures or consultancy from Bayer Healthcare, Biogen, Baxalta/Shire, CSL Behring, Grifols, MedDay, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, and Teva. His institution received research support from Bayer Healthcare, Biogen, Genzyme, Merck-Serono, Novartis, and Teva. He is on the editorial board of PLoS ONE and Multiple Sclerosis International.
O.A.: nothing to disclose.
S.M.: nothing to disclose.
C.C.G. received speaker honoraria and travel expenses for attending meetings from Biogen, Euroimmun, Genzyme, and Bayer Health Care. Her work is funded by the German Ministry for Education and Research (BMBF; 01GI1603A), the German Research Foundation (DFG; GR3946/3-1 and SFB/Transregio 128 A09), and the European Union (Horizon2020, RESTORE).
A.B. received personal compensation from Merck Serono, Biogen, Bayer Vital, Novartis, TEVA, Roche and Sanofi/Genzyme and grants for congress trips and participation from Biogen, TEVA, Novartis, Sanofi/Genzyme and Merck Serono.
B.W. reports grants from German Ministry of Education and Research, grants from Dietmar Hopp Foundation, grants from Klaus Tschira Foundation, personal fees from Bayer Healthcare, personal fees from Biogen, grants and personal fees from Merck Serono, grants and personal fees from Novartis, grants and personal fees from Sanofi Genzyme, grants and personal fees from TEVA, outside the submitted work.
F.L.: nothing to disclose.
M.S.: nothing to disclose.
M.P.: nothing to disclose.
G.A.: nothing to disclose.
F.W. served on the scientific advisory board of Genzyme and Novartis; received travel funding and/or speaker honoraria from Biogen, Teva, Merck Serono, Novartis, and Pfizer; is employed by Sana; and received research support from Merck Serono, Novartis, and MBMF.
M.U.: nothing to disclose.
F.B.: nothing to disclose.
K.R. was supported by the German Ministry of Education and Research (BMBF/KKNMS, Competence Network Multiple Sclerosis) and has received research support from Novartis and Merck Serono as well as speaking fees and travel grants from Guthy Jackson Charitable Foundation, Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, Roche and Novartis.
D.B.: nothing to disclose.
N.R.: nothing to disclose.
U.K.Z.: nothing to disclose.
A.H.: nothing to disclose.
C.L. received a research grant by the German Federal Ministry for Education
and Research, BMBF, German Competence Network Multiple Sclerosis (KKNMS),
grant no.01GI1601I, has received consulting and speaker´s honoraria from
Biogen Idec, Bayer Schering, Daiichi Sanykyo, Merck Serono, Novartis,
Sanofi, Genzyme and TEVA.
H-P.H.: nothing to disclose.
F.T.B. has received personal compensation for speaking and attending advisory boards from Actelion, Bayer, Biogen, Genzyme, Merck, Novartis, Teva and Roche; financial support, through his institution, to attend scientific meetings or for investigator initiated studies from Actelion, Bayer, Biogen, Genzyme, Merck, Novartis and Teva.
C.W. received personal fees for consulting: Biogen, Novartis (none since 8/2016). Consulting for the European Medicines Agency, and the Institute for Quality and Efficiency in Health Care, Germany.
F.Z.: nothing to disclose.
H.W. received honoraria for scientific advisory boards/steering committees from Biogen, Evgen, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG, and Sanofi-Genzyme. He received speaker honoraria and travel support for attending meetings from Actelion, Alexion, Biogen, Cognomed, F. Hoffmann-La Roche Ltd., Gemeinnützige Hertie-Stiftung, Lundbeck, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, TEVA, and WebMD Globa. HW received compensation as a consultant from Abbvie, Actelion, Biogen, Immunic AG, Novartis, Roche, RxMx, and Sanofi-Genzyme. He also received research support from the German Ministry for Education and Research (BMBF), Deutsche Forschungsgesellschaft (DFG), Else Kröner Fresenius Foundation, European Union, Fresenius Foundation, Hertie Foundation, NRW Ministry of Education and Research, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, RE Children's Foundation, PML Consortium, Swiss MS Society, Biogen GmbH, GlaxoSmithKline GmbH, Roche Pharma AG, and Sanofi-Genzyme.
B.H.: nothing to disclose.
R.G.: nothing to disclose.
H.T. received funding for research projects, lectures and travel from Bayer, Biogen, Genzyme, Fresenius, Merck, Novartis, Roche, Siemens Health Diagnostics, Teva, and received research support from DMSG, Hertie-Stiftung, BMBF, University of Ulm and Landesstiftung BW.
Abstract: P1169
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background and Objectives: To evaluate and validate a subset of candidate biomarkers in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) we prospectively characterized IgG-oligoclonal bands (OCBs), intrathecal IgG antibodies against measles, rubella and varicella zoster viruses (MRZ reaction), CXCL13, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP).
Methods: Patients were recruited from multiple specialized MS centres in Germany. Inclusion criteria were 1) first manifestation of clinically isolated syndrome (CIS) or MS, 2) availability of baseline CSF data, and 3) availability of baseline and follow-up MRI data. CXCL13, NfL and GFAP were measured using classical ELISA, the MRZ reaction was determined by a multiplexing technique. All biomarkers were characterized by comparing their levels to diagnosis, T2 and gadolinium enhanced (GD+) lesions and EDSS at baseline. To evaluate their predictive value, levels were compared to disease progression by clinical or MRI signs and EDSS development within two years.
Results: We collected data from 193 patients with a median age at clinical onset of 31 years (IQR 26-40) and a proportion of females of 75 % (144/193).
At disease onset 91/193 (47%) patients were diagnosed with a CIS and 102/193 (53 %) fulfilled the McDonald 2005 criteria for MS.
OCBs were detectable in 81/91 (89 %) of CIS and 93/102 (91 %) of MS patients and the MRZ reaction in 37/91 (40 %) of CIS and 51/102 (52 %) of MS patients. Only NfL CSF levels were slightly higher in MS compared to CIS patients (p-value= 0.04). CXCL13 and NfL were higher in patients with GD+ lesions compared to patients without GD+ lesion (p-values= 0.092 and 0.011, respectively). Additionally, NfL showed a weak association with EDSS (Spearman rho= 0.18, p-value= 0.015) and with 9 or more T2 lesions compared to 1-8 T2 lesions (p-value< 0.0001). Higher levels of NfL predicted disease progression indicated by MRI within two years (p-value= 0.015) and GFAP levels showed a tendency to be higher if patients had an increase of their EDSS within two years (p-value= 0.05).
Conclusion: Our data show that especially NfL is an informative marker for structural damage, disease severity and progression in MS and CXCL13 may be a marker of disease activity. GFAP is not differentially regulated in the early phase of MS but might be associated with disease progression indicated by EDSS.
Disclosure: A.H.: nothing to disclose.
M.O. reports grants from BMBF (FTLDc), grants from Thierry Latran foundation, grants
from ALS association, grants from Foundation State Baden-Wuerttemberg, grants from Boehringer Ingelheim University Ulm Institute, grants from EU (Fairpark), personal fees from Teva, Fujirebio, personal fees from Axon, Roche, Neuroallianz, outside the submitted work.
B.T.: nothing to disclose.
M.S. has received honoraria for scientific lectures or consultancy from Bayer Healthcare, Biogen, Baxalta/Shire, CSL Behring, Grifols, MedDay, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, and Teva. His institution received research support from Bayer Healthcare, Biogen, Genzyme, Merck-Serono, Novartis, and Teva. He is on the editorial board of PLoS ONE and Multiple Sclerosis International.
O.A.: nothing to disclose.
S.M.: nothing to disclose.
C.C.G. received speaker honoraria and travel expenses for attending meetings from Biogen, Euroimmun, Genzyme, and Bayer Health Care. Her work is funded by the German Ministry for Education and Research (BMBF; 01GI1603A), the German Research Foundation (DFG; GR3946/3-1 and SFB/Transregio 128 A09), and the European Union (Horizon2020, RESTORE).
A.B. received personal compensation from Merck Serono, Biogen, Bayer Vital, Novartis, TEVA, Roche and Sanofi/Genzyme and grants for congress trips and participation from Biogen, TEVA, Novartis, Sanofi/Genzyme and Merck Serono.
B.W. reports grants from German Ministry of Education and Research, grants from Dietmar Hopp Foundation, grants from Klaus Tschira Foundation, personal fees from Bayer Healthcare, personal fees from Biogen, grants and personal fees from Merck Serono, grants and personal fees from Novartis, grants and personal fees from Sanofi Genzyme, grants and personal fees from TEVA, outside the submitted work.
F.L.: nothing to disclose.
M.S.: nothing to disclose.
M.P.: nothing to disclose.
G.A.: nothing to disclose.
F.W. served on the scientific advisory board of Genzyme and Novartis; received travel funding and/or speaker honoraria from Biogen, Teva, Merck Serono, Novartis, and Pfizer; is employed by Sana; and received research support from Merck Serono, Novartis, and MBMF.
M.U.: nothing to disclose.
F.B.: nothing to disclose.
K.R. was supported by the German Ministry of Education and Research (BMBF/KKNMS, Competence Network Multiple Sclerosis) and has received research support from Novartis and Merck Serono as well as speaking fees and travel grants from Guthy Jackson Charitable Foundation, Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, Roche and Novartis.
D.B.: nothing to disclose.
N.R.: nothing to disclose.
U.K.Z.: nothing to disclose.
A.H.: nothing to disclose.
C.L. received a research grant by the German Federal Ministry for Education
and Research, BMBF, German Competence Network Multiple Sclerosis (KKNMS),
grant no.01GI1601I, has received consulting and speaker´s honoraria from
Biogen Idec, Bayer Schering, Daiichi Sanykyo, Merck Serono, Novartis,
Sanofi, Genzyme and TEVA.
H-P.H.: nothing to disclose.
F.T.B. has received personal compensation for speaking and attending advisory boards from Actelion, Bayer, Biogen, Genzyme, Merck, Novartis, Teva and Roche; financial support, through his institution, to attend scientific meetings or for investigator initiated studies from Actelion, Bayer, Biogen, Genzyme, Merck, Novartis and Teva.
C.W. received personal fees for consulting: Biogen, Novartis (none since 8/2016). Consulting for the European Medicines Agency, and the Institute for Quality and Efficiency in Health Care, Germany.
F.Z.: nothing to disclose.
H.W. received honoraria for scientific advisory boards/steering committees from Biogen, Evgen, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG, and Sanofi-Genzyme. He received speaker honoraria and travel support for attending meetings from Actelion, Alexion, Biogen, Cognomed, F. Hoffmann-La Roche Ltd., Gemeinnützige Hertie-Stiftung, Lundbeck, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, TEVA, and WebMD Globa. HW received compensation as a consultant from Abbvie, Actelion, Biogen, Immunic AG, Novartis, Roche, RxMx, and Sanofi-Genzyme. He also received research support from the German Ministry for Education and Research (BMBF), Deutsche Forschungsgesellschaft (DFG), Else Kröner Fresenius Foundation, European Union, Fresenius Foundation, Hertie Foundation, NRW Ministry of Education and Research, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, RE Children's Foundation, PML Consortium, Swiss MS Society, Biogen GmbH, GlaxoSmithKline GmbH, Roche Pharma AG, and Sanofi-Genzyme.
B.H.: nothing to disclose.
R.G.: nothing to disclose.
H.T. received funding for research projects, lectures and travel from Bayer, Biogen, Genzyme, Fresenius, Merck, Novartis, Roche, Siemens Health Diagnostics, Teva, and received research support from DMSG, Hertie-Stiftung, BMBF, University of Ulm and Landesstiftung BW.