Contributions
Abstract: EP1605
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Increased levels of Neurofilament light protein (NFL) in cerebrospinal fluid (CSF) indicate axonal degeneration and are associated with disease activity in MS. The concentration of CSF-CXCL13 has strong association with neuroinflammation and B-cell infiltration. In MS, CSF-CXCL13 levels correlate to CSF-NFL levels, supporting a connection between inflammation and axonal injury in the pathogenesis of MS.
Objective: To investigate the degree of inflammation and axonal injury in patients of different MS phenotypes MS by comparing the changes in the CSF levels of NFL and CXCL13 in patients with relapsing-remitting (RRMS) and progressive multiple sclerosis (PrMS) during disease activity and during disease modifying treatments (DMTs).
Methods: We included 202 RRMS and 84 PrMS patients, of those 95 RRMS and 47 PrMS were followed for 12 months. CXCL13 and NFL were determined by ELISA. Disease activity was defined as a relapse within 3 months prior to sampling and/or one or more gadolinium (Gd) contrast enhancing lesions on MRI. The increased levels of NFL and CXCL13 were defined as levels above the following reference values: CSF-NLF reference range for different ages are < 30 years: < 380ng/L; 30-40 years: < 560 ng / L; 40 years- < 60 years: < 890 ng / L; > = 60 years: < 1850 ng / L. CSF-CXCL13 reference value is > 7.8 ng / L.
Results: In RRMS and PrMS with disease activity, NFL levels were increased in 63.6% and 64.5%, and CXCL13 levels were increased in 53.3% and 58.1%, and both were increased in 34.1% and 45.2%, respectively. In RRMS and PrMS without disease activity, NFL levels were increased in 34.1% and 34.7%, and CXCL13 levels were increased in 14.1% and 17%, and both were increased in 8% and 11.9%, respectively. In 4.5% RRMS and 9.1% PrMS with low CSF levels of NFL and CXCL13 had signs of ongoing disease activity.
The treatment with various DMTs decreased the levels of NFL and CXCL13 in 78% RRMS (p< 0.001 and p< 0.001) and in 64% PrMS (p=0.014 and p=0.063), respectively.
Discussion: The increased CSF levels of NFL and CXCL13 in MS patients without a recent relapse and without contrast enhancing lesions on MRI indicate a residual disease activity not detected clinically or by MRI. Further, DMTs reduced NFL and CXCL13 levels supporting treatment effects on both inflammation and degeneration. Thus, CSF biomarkers add information that might facilitate the monitoring of disease activity and therapeutic decision in MS patients.
Disclosure:
LN has no disclosures.
HZ is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg and has served at advisory boards for Roche Diagnostics, Eli Lilly and Pharmasum Therapeuticss.
MA has received compensation for lectures and/or advisory boards from Biogen, Genzyme, and Novartis.
CM has received honoraria for lectures and advisory boards from Biogen and Novartis.
AS has served on advisory board for Sanofi-Genzyme and has received travel funding from Biogen Idec.
KB has served as a consultant or at advisory boards for Alzheon, Eli-Lilly, Fujirebio Europe, IBL International and Roche Diagnostics, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg.
JL has received travel support and/or lecture honoraria from Biogen, Novartis, Teva and Genzyme/SanofiAventis; has served on scientific advisory boards for Almirall, Teva, Biogen, Novartis and Genzyme/SanofiAventis; serves on the editorial board of the Acta Neurologica Scandinavica; has received unconditional research grants from Biogen, Novartis and Teva.
Abstract: EP1605
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Increased levels of Neurofilament light protein (NFL) in cerebrospinal fluid (CSF) indicate axonal degeneration and are associated with disease activity in MS. The concentration of CSF-CXCL13 has strong association with neuroinflammation and B-cell infiltration. In MS, CSF-CXCL13 levels correlate to CSF-NFL levels, supporting a connection between inflammation and axonal injury in the pathogenesis of MS.
Objective: To investigate the degree of inflammation and axonal injury in patients of different MS phenotypes MS by comparing the changes in the CSF levels of NFL and CXCL13 in patients with relapsing-remitting (RRMS) and progressive multiple sclerosis (PrMS) during disease activity and during disease modifying treatments (DMTs).
Methods: We included 202 RRMS and 84 PrMS patients, of those 95 RRMS and 47 PrMS were followed for 12 months. CXCL13 and NFL were determined by ELISA. Disease activity was defined as a relapse within 3 months prior to sampling and/or one or more gadolinium (Gd) contrast enhancing lesions on MRI. The increased levels of NFL and CXCL13 were defined as levels above the following reference values: CSF-NLF reference range for different ages are < 30 years: < 380ng/L; 30-40 years: < 560 ng / L; 40 years- < 60 years: < 890 ng / L; > = 60 years: < 1850 ng / L. CSF-CXCL13 reference value is > 7.8 ng / L.
Results: In RRMS and PrMS with disease activity, NFL levels were increased in 63.6% and 64.5%, and CXCL13 levels were increased in 53.3% and 58.1%, and both were increased in 34.1% and 45.2%, respectively. In RRMS and PrMS without disease activity, NFL levels were increased in 34.1% and 34.7%, and CXCL13 levels were increased in 14.1% and 17%, and both were increased in 8% and 11.9%, respectively. In 4.5% RRMS and 9.1% PrMS with low CSF levels of NFL and CXCL13 had signs of ongoing disease activity.
The treatment with various DMTs decreased the levels of NFL and CXCL13 in 78% RRMS (p< 0.001 and p< 0.001) and in 64% PrMS (p=0.014 and p=0.063), respectively.
Discussion: The increased CSF levels of NFL and CXCL13 in MS patients without a recent relapse and without contrast enhancing lesions on MRI indicate a residual disease activity not detected clinically or by MRI. Further, DMTs reduced NFL and CXCL13 levels supporting treatment effects on both inflammation and degeneration. Thus, CSF biomarkers add information that might facilitate the monitoring of disease activity and therapeutic decision in MS patients.
Disclosure:
LN has no disclosures.
HZ is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg and has served at advisory boards for Roche Diagnostics, Eli Lilly and Pharmasum Therapeuticss.
MA has received compensation for lectures and/or advisory boards from Biogen, Genzyme, and Novartis.
CM has received honoraria for lectures and advisory boards from Biogen and Novartis.
AS has served on advisory board for Sanofi-Genzyme and has received travel funding from Biogen Idec.
KB has served as a consultant or at advisory boards for Alzheon, Eli-Lilly, Fujirebio Europe, IBL International and Roche Diagnostics, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg.
JL has received travel support and/or lecture honoraria from Biogen, Novartis, Teva and Genzyme/SanofiAventis; has served on scientific advisory boards for Almirall, Teva, Biogen, Novartis and Genzyme/SanofiAventis; serves on the editorial board of the Acta Neurologica Scandinavica; has received unconditional research grants from Biogen, Novartis and Teva.