Contributions
Abstract: EP1285
Type: ePoster
Abstract Category: Clinical aspects of MS - 1 Diagnosis and differential diagnosis
Background: Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are relapsing inflammatory diseases of the CNS. NMOSD is caused by antibodies against aquaporin 4 (AQP4) in the majority of cases.
Objectives: To examine if soluble biomarkers of endothelial stress, cytokines, and chemokines can differentiate AQP4+NMOSD from relapsing-remitting multiple sclerosis (RRMS) and correlate with the levels of anti-AQP4.
Methods: We examined serum from 46 patients with anti-AQP4+NMOSD, 30 patients with RRMS and 22 healthy subjects (HS). IgG and IgM anti-AQP4 antibodies were determined by cell-based flow cytometry assays with human glioblastoma cell line stably transduced using a lentiviral vector to overexpress human AQP4-M23. Twenty-six biomarkers were measured by the Mesoscale Discovery technique.
Results: Hierarchical clustering was able to differentiate AQP4+NMOSD and RRMS. Correlation among biomarkers defined major clusters of endothelial stress (VCAM, ICAM, SAA), IL-12p40/IL-23 and IL-16, and an inflammatory cluster including IL-8, IL-1b, TNF-a, IL-6, IL-12p70. Seventeen biomarkers were differently expressed in AQP4+NMOSD compared to RRMS; among them, IL-6, IL-8., IL-16, and IL-12p40/IL-23 were significantly increased in AQP4+NMOSD and MS compared to HS. Concentration of biomarkers did not correlate levels of AQP4 IgG in the sera. Decision tree defined the endothelial cluster important in AQP4+NMOSD and RRMS differentiation, and the IL-12p40/IL-23/IL-16 cluster further differentiating RRMS from HS.
Conclusion: Elevated levels of biomarkers and biomarker cluster reflecting endothelial stress (VCAM, ICAM, IL-6, IL-8) may differentiate AQP4+NMOSD from RRMS, while Th17 expansion may be important in both diseases reflected by elevated levels of IL-23 compared to HS.
Disclosure:
HHN:has received grant support and consultation fees from Biogen Idec, UCB Nordic, Novartis, Teva and Genzyme as well as the Danish Multiple Sclerosis Society and the region of Southern Denmark Research Fund.
TS:has received grant support and consultation fees from Biogen Idec, Novartis, Teva and Genzyme as well as the Danish Multiple Sclerosis Society and the region of Southern Denmark Research Fund.
ZI: has received grant support and consultation fees from Biogen Idec, Novartis, Teva and Genzyme as well as the Danish Multiple Sclerosis Society and the region of Southern Denmark Research Fund.
TP: has received grant support and consultation fees from Biogen Idec, Novartis, Teva and Genzyme as well as the Danish Multiple Sclerosis Society.
GD: has received grant support and consultation fees from Biogen Idec, Novartis, Teva and Genzyme.
BH: HHN has received grant support and consultation fees from Biogen Idec, Roche Novartis, Teva and Genzyme.
SK: nothing to declare
TF: nothing to declare
TC: nothing to declare
GL: nothing to declare
MS: nothing to declare
TM: nothing to declare
JB: nothing to declare
Abstract: EP1285
Type: ePoster
Abstract Category: Clinical aspects of MS - 1 Diagnosis and differential diagnosis
Background: Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are relapsing inflammatory diseases of the CNS. NMOSD is caused by antibodies against aquaporin 4 (AQP4) in the majority of cases.
Objectives: To examine if soluble biomarkers of endothelial stress, cytokines, and chemokines can differentiate AQP4+NMOSD from relapsing-remitting multiple sclerosis (RRMS) and correlate with the levels of anti-AQP4.
Methods: We examined serum from 46 patients with anti-AQP4+NMOSD, 30 patients with RRMS and 22 healthy subjects (HS). IgG and IgM anti-AQP4 antibodies were determined by cell-based flow cytometry assays with human glioblastoma cell line stably transduced using a lentiviral vector to overexpress human AQP4-M23. Twenty-six biomarkers were measured by the Mesoscale Discovery technique.
Results: Hierarchical clustering was able to differentiate AQP4+NMOSD and RRMS. Correlation among biomarkers defined major clusters of endothelial stress (VCAM, ICAM, SAA), IL-12p40/IL-23 and IL-16, and an inflammatory cluster including IL-8, IL-1b, TNF-a, IL-6, IL-12p70. Seventeen biomarkers were differently expressed in AQP4+NMOSD compared to RRMS; among them, IL-6, IL-8., IL-16, and IL-12p40/IL-23 were significantly increased in AQP4+NMOSD and MS compared to HS. Concentration of biomarkers did not correlate levels of AQP4 IgG in the sera. Decision tree defined the endothelial cluster important in AQP4+NMOSD and RRMS differentiation, and the IL-12p40/IL-23/IL-16 cluster further differentiating RRMS from HS.
Conclusion: Elevated levels of biomarkers and biomarker cluster reflecting endothelial stress (VCAM, ICAM, IL-6, IL-8) may differentiate AQP4+NMOSD from RRMS, while Th17 expansion may be important in both diseases reflected by elevated levels of IL-23 compared to HS.
Disclosure:
HHN:has received grant support and consultation fees from Biogen Idec, UCB Nordic, Novartis, Teva and Genzyme as well as the Danish Multiple Sclerosis Society and the region of Southern Denmark Research Fund.
TS:has received grant support and consultation fees from Biogen Idec, Novartis, Teva and Genzyme as well as the Danish Multiple Sclerosis Society and the region of Southern Denmark Research Fund.
ZI: has received grant support and consultation fees from Biogen Idec, Novartis, Teva and Genzyme as well as the Danish Multiple Sclerosis Society and the region of Southern Denmark Research Fund.
TP: has received grant support and consultation fees from Biogen Idec, Novartis, Teva and Genzyme as well as the Danish Multiple Sclerosis Society.
GD: has received grant support and consultation fees from Biogen Idec, Novartis, Teva and Genzyme.
BH: HHN has received grant support and consultation fees from Biogen Idec, Roche Novartis, Teva and Genzyme.
SK: nothing to declare
TF: nothing to declare
TC: nothing to declare
GL: nothing to declare
MS: nothing to declare
TM: nothing to declare
JB: nothing to declare