Elevated serum levels of bone morphogenetic protein-9 are associated with better outcome in AQP4-IgG seropositive NMOSD

Abstract Lymphatic drainage in the central nervous system is regulated by meningeal lymphatic vasculature, and recurrent neuroinflammation alters lymphatic vessel remodeling. Patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD) were reported to demonstrat...

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Main Authors: Hiroki Masuda, Masahiro Mori, Akiyuki Uzawa, Tomohiko Uchida, Mayumi Muto, Ryohei Ohtani, Reiji Aoki, Satoshi Kuwabara
Format: Article
Language:English
Published: Nature Portfolio 2023-03-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-30594-z
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author Hiroki Masuda
Masahiro Mori
Akiyuki Uzawa
Tomohiko Uchida
Mayumi Muto
Ryohei Ohtani
Reiji Aoki
Satoshi Kuwabara
author_facet Hiroki Masuda
Masahiro Mori
Akiyuki Uzawa
Tomohiko Uchida
Mayumi Muto
Ryohei Ohtani
Reiji Aoki
Satoshi Kuwabara
author_sort Hiroki Masuda
collection DOAJ
description Abstract Lymphatic drainage in the central nervous system is regulated by meningeal lymphatic vasculature, and recurrent neuroinflammation alters lymphatic vessel remodeling. Patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD) were reported to demonstrate worse outcomes compared with patients with anti-myelin oligodendrocyte glycoprotein-associated disorders (MOGAD). This study aimed to investigate the serum cytokines relevant to vascular remodeling after attacks and their prognostic role in patients with AQP4 + NMOSD. This study measured the serum levels of 12 cytokines relevant to vascular remodeling, including bone morphogenetic protein-9 (BMP-9) and leptin, in 20 patients with AQP4 + NMOSD and 17 healthy controls (HCs). Disease controls included 18 patients with MOGAD. Serum and cerebrospinal fluid interleukin-6 levels were also measured. Clinical severity was evaluated with Kurtzke’s Expanded Disability Status Scale (EDSS). Compared with HCs, patients with AQP4 + NMOSD showed higher BMP-9 (median; 127 vs. 80.7 pg/mL; P = 0.0499) and leptin levels (median; 16,081 vs. 6770 pg/mL; P = 0.0224), but not those with MOGAD. Better improvement in EDSS at 6 months was associated with baseline BMP-9 levels in patients with AQP4 + NMOSD (Spearman’s rho =  − 0.47; P = 0.037). Serum BMP-9 is upregulated at relapse and may contribute to vascular remodeling in AQP4 + NMOSD. Serum BMP-9 levels could predict clinical recovery 6 months after the attack.
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spelling doaj.art-e5008498960642a48fbdcea2dcd6858b2023-03-22T11:02:36ZengNature PortfolioScientific Reports2045-23222023-03-011311910.1038/s41598-023-30594-zElevated serum levels of bone morphogenetic protein-9 are associated with better outcome in AQP4-IgG seropositive NMOSDHiroki Masuda0Masahiro Mori1Akiyuki Uzawa2Tomohiko Uchida3Mayumi Muto4Ryohei Ohtani5Reiji Aoki6Satoshi Kuwabara7Department of Neurology, Graduate School of Medicine, Chiba UniversityDepartment of Neurology, Graduate School of Medicine, Chiba UniversityDepartment of Neurology, Graduate School of Medicine, Chiba UniversityDepartment of Neurology, Graduate School of Medicine, Chiba UniversityDepartment of Neurology, Graduate School of Medicine, Chiba UniversityDepartment of Neurology, Graduate School of Medicine, Chiba UniversityDepartment of Neurology, Graduate School of Medicine, Chiba UniversityDepartment of Neurology, Graduate School of Medicine, Chiba UniversityAbstract Lymphatic drainage in the central nervous system is regulated by meningeal lymphatic vasculature, and recurrent neuroinflammation alters lymphatic vessel remodeling. Patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD) were reported to demonstrate worse outcomes compared with patients with anti-myelin oligodendrocyte glycoprotein-associated disorders (MOGAD). This study aimed to investigate the serum cytokines relevant to vascular remodeling after attacks and their prognostic role in patients with AQP4 + NMOSD. This study measured the serum levels of 12 cytokines relevant to vascular remodeling, including bone morphogenetic protein-9 (BMP-9) and leptin, in 20 patients with AQP4 + NMOSD and 17 healthy controls (HCs). Disease controls included 18 patients with MOGAD. Serum and cerebrospinal fluid interleukin-6 levels were also measured. Clinical severity was evaluated with Kurtzke’s Expanded Disability Status Scale (EDSS). Compared with HCs, patients with AQP4 + NMOSD showed higher BMP-9 (median; 127 vs. 80.7 pg/mL; P = 0.0499) and leptin levels (median; 16,081 vs. 6770 pg/mL; P = 0.0224), but not those with MOGAD. Better improvement in EDSS at 6 months was associated with baseline BMP-9 levels in patients with AQP4 + NMOSD (Spearman’s rho =  − 0.47; P = 0.037). Serum BMP-9 is upregulated at relapse and may contribute to vascular remodeling in AQP4 + NMOSD. Serum BMP-9 levels could predict clinical recovery 6 months after the attack.https://doi.org/10.1038/s41598-023-30594-z
spellingShingle Hiroki Masuda
Masahiro Mori
Akiyuki Uzawa
Tomohiko Uchida
Mayumi Muto
Ryohei Ohtani
Reiji Aoki
Satoshi Kuwabara
Elevated serum levels of bone morphogenetic protein-9 are associated with better outcome in AQP4-IgG seropositive NMOSD
Scientific Reports
title Elevated serum levels of bone morphogenetic protein-9 are associated with better outcome in AQP4-IgG seropositive NMOSD
title_full Elevated serum levels of bone morphogenetic protein-9 are associated with better outcome in AQP4-IgG seropositive NMOSD
title_fullStr Elevated serum levels of bone morphogenetic protein-9 are associated with better outcome in AQP4-IgG seropositive NMOSD
title_full_unstemmed Elevated serum levels of bone morphogenetic protein-9 are associated with better outcome in AQP4-IgG seropositive NMOSD
title_short Elevated serum levels of bone morphogenetic protein-9 are associated with better outcome in AQP4-IgG seropositive NMOSD
title_sort elevated serum levels of bone morphogenetic protein 9 are associated with better outcome in aqp4 igg seropositive nmosd
url https://doi.org/10.1038/s41598-023-30594-z
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