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

• Published in: Scientific reports Vol. 13; no. 1; p. 3538
• Main Authors: Masuda, Hiroki, Mori, Masahiro, Uzawa, Akiyuki, Uchida, Tomohiko, Muto, Mayumi, Ohtani, Ryohei, Aoki, Reiji, Kuwabara, Satoshi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.03.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 631/250/127; 631/250/371; 692/617; 692/617/375; Aquaporin 4; Aquaporin 4 - immunology; Bone morphogenetic protein 9; Bone morphogenetic proteins; Bone remodeling; Central nervous system; Cerebrospinal fluid; Cytokines; Growth Differentiation Factor 2; Humanities and Social Sciences; Humans; Immunoglobulin G; Inflammation; Interleukin 6; Leptin; Lymphatic drainage; multidisciplinary; Myelin; Myelin-Oligodendrocyte Glycoprotein; Neuromyelitis; Neuromyelitis Optica; Oligodendrocyte-myelin glycoprotein; Science; Science (multidisciplinary); Serum levels; Vascular Remodeling
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-30594-z

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.