Contributions
Abstract: EP1569
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Breakdown of the blood-brain barrier (BBB) is a key pathological feature of multiple sclerosis (MS). We previously reported the effect of sera from MS patients on the BBB dysfunction. We also published the association between blood-brain barrier (BBB) dysfunction and glucose-regulated protein 78 (GRP 78) autoantibodies in neuromyelitis optica (NMO).
Objective: The purpose of this study is to clarify the effect of immunoglobulin G (IgG) from MS patients on the BBB-endothelial cell activation. We observed the association among the clinical phenotype/disease activity, positivity of GRP78 antibodies and BBB disruption in MS.
Methods: We purified serum IgG from 38 sera with MS patients [9 MS in the acute phase (acute MS), 14 MS in the secondary/primary progressive phase (progressive MS), 15 MS in stable stage (stable MS)]. IgGs from 10 healthy volunteers and 11 disease controls were used as controls. IgG was exposed to the human brain microvascular endothelial cells (TY10) and the amount of nuclear NF-κB p65 positive cells as a marker of endothelial cell activation was analyzed using a high-content imaging system. Presence of GRP78 antibodies from patient IgGs was detected by western blots. Positivity of CSF oligoclonal IgG band (OCB) from MS patients was also evaluated.
Results: IgG in progressive/acute MS group significantly induced the nuclear translocation of NF-κB p65 compared to those from stable MS group and healthy/disease control group. There is no significant difference in the positive rate of GRP78 antibodies among progressive MS, acute MS, stable MS, disease controls and healthy controls. No association was observed in the number of nuclear NF-κB p65 positive cells induced by IgG between positive and negative for OCB in MS patients.
Conclusion: Endothelial cell activation induced by IgG incubation was observed in not only NMO but also MS patients and associated with acute/progressive MS stage. The positivity of GRP78 antibodies is not associated with BBB disruption in MS, unlike NMO, suggesting that unknown molecules other than GRP78 antibodies that contribute to BBB breakdown may be present in MS sera.
Disclosure: nothing to disclose
Abstract: EP1569
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Breakdown of the blood-brain barrier (BBB) is a key pathological feature of multiple sclerosis (MS). We previously reported the effect of sera from MS patients on the BBB dysfunction. We also published the association between blood-brain barrier (BBB) dysfunction and glucose-regulated protein 78 (GRP 78) autoantibodies in neuromyelitis optica (NMO).
Objective: The purpose of this study is to clarify the effect of immunoglobulin G (IgG) from MS patients on the BBB-endothelial cell activation. We observed the association among the clinical phenotype/disease activity, positivity of GRP78 antibodies and BBB disruption in MS.
Methods: We purified serum IgG from 38 sera with MS patients [9 MS in the acute phase (acute MS), 14 MS in the secondary/primary progressive phase (progressive MS), 15 MS in stable stage (stable MS)]. IgGs from 10 healthy volunteers and 11 disease controls were used as controls. IgG was exposed to the human brain microvascular endothelial cells (TY10) and the amount of nuclear NF-κB p65 positive cells as a marker of endothelial cell activation was analyzed using a high-content imaging system. Presence of GRP78 antibodies from patient IgGs was detected by western blots. Positivity of CSF oligoclonal IgG band (OCB) from MS patients was also evaluated.
Results: IgG in progressive/acute MS group significantly induced the nuclear translocation of NF-κB p65 compared to those from stable MS group and healthy/disease control group. There is no significant difference in the positive rate of GRP78 antibodies among progressive MS, acute MS, stable MS, disease controls and healthy controls. No association was observed in the number of nuclear NF-κB p65 positive cells induced by IgG between positive and negative for OCB in MS patients.
Conclusion: Endothelial cell activation induced by IgG incubation was observed in not only NMO but also MS patients and associated with acute/progressive MS stage. The positivity of GRP78 antibodies is not associated with BBB disruption in MS, unlike NMO, suggesting that unknown molecules other than GRP78 antibodies that contribute to BBB breakdown may be present in MS sera.
Disclosure: nothing to disclose