Contributions
Abstract: P443
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Immunology
Objective: To elucidate the potential role of soluble CD40 ligand (sCD40L) in blood-brain barrier (BBB) disruption in patients with multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) mice.
Methods: Serum and cerebrospinal fluid (CSF) sCD40L levels in 29 patients with MS and 27 disease controls (DCs) were measured using multiplex immunoassay. Samples from patients with MS were obtained within 50 days after the onset of an attack. Clinical and laboratory profiles including CSF/serum albumin ratio (Qalb), a marker of BBB breakdown, were also investigated. In addition, recombinant mouse sCD40L was used in mice with EAE in vivo and the human brain microvascular endothelial cell (HBMEC)-based BBB in vitro model. Permeability coefficient (Pe, cm/min) was calculated by the sodium fluorescein permeability assay in the HBMEC/ci18-based in vitro BBB method.
Results: Serum sCD40L levels, which was higher in patients with MS than in DCs [median, 2480 versus 786 pg/mL; interquartile range (IQR), 2590 vs 1379; P = 0.046], was positively correlated with Qalb (Kendall's tau-b = 0.29, P = 0.044). Although CSF sCD40L levels were higher in patients with MS than in DCs (median 38.5 vs 4.8 pg/mL, IQR 45.7 vs 23.6, P = 0.002), no correlation was found between CSF sCD40L and Qalb. EAE scores of mice receiving high-dose sCD40L were worse than those receiving low-dose sCD40L and controls. Pe was increased by sCD40L treatment in the HBMEC-based BBB model (median, 2.43 vs 1.78 10−3 cm/min; IQR, 0.85 vs 0.64; P = 0.032).
Conclusions: Soluble CD40L may facilitate inflammation in MS and EAE by BBB disruption.
Disclosure: Hiroki Masuda: This study was supported by JSPS KAKENHI (Grant Number
17K16109).
Masahiro Mori: nothing to disclose.
Tomohiko Uchida: nothing to disclose.
Akiyuki Uzawa: nothing to disclose.
Ryohei Ohtani: nothing to disclose.
Satoshi Kuwabara: nothing to disclose.
Abstract: P443
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Immunology
Objective: To elucidate the potential role of soluble CD40 ligand (sCD40L) in blood-brain barrier (BBB) disruption in patients with multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) mice.
Methods: Serum and cerebrospinal fluid (CSF) sCD40L levels in 29 patients with MS and 27 disease controls (DCs) were measured using multiplex immunoassay. Samples from patients with MS were obtained within 50 days after the onset of an attack. Clinical and laboratory profiles including CSF/serum albumin ratio (Qalb), a marker of BBB breakdown, were also investigated. In addition, recombinant mouse sCD40L was used in mice with EAE in vivo and the human brain microvascular endothelial cell (HBMEC)-based BBB in vitro model. Permeability coefficient (Pe, cm/min) was calculated by the sodium fluorescein permeability assay in the HBMEC/ci18-based in vitro BBB method.
Results: Serum sCD40L levels, which was higher in patients with MS than in DCs [median, 2480 versus 786 pg/mL; interquartile range (IQR), 2590 vs 1379; P = 0.046], was positively correlated with Qalb (Kendall's tau-b = 0.29, P = 0.044). Although CSF sCD40L levels were higher in patients with MS than in DCs (median 38.5 vs 4.8 pg/mL, IQR 45.7 vs 23.6, P = 0.002), no correlation was found between CSF sCD40L and Qalb. EAE scores of mice receiving high-dose sCD40L were worse than those receiving low-dose sCD40L and controls. Pe was increased by sCD40L treatment in the HBMEC-based BBB model (median, 2.43 vs 1.78 10−3 cm/min; IQR, 0.85 vs 0.64; P = 0.032).
Conclusions: Soluble CD40L may facilitate inflammation in MS and EAE by BBB disruption.
Disclosure: Hiroki Masuda: This study was supported by JSPS KAKENHI (Grant Number
17K16109).
Masahiro Mori: nothing to disclose.
Tomohiko Uchida: nothing to disclose.
Akiyuki Uzawa: nothing to disclose.
Ryohei Ohtani: nothing to disclose.
Satoshi Kuwabara: nothing to disclose.