Xu Wang1, Wenyu Jiao1, Meng Lin1, Chao Lu1, Caiyun Liu1, Ying Wang2, Di Ma1, Xiuzhe Wang3, Ping Yin1, Jiachun Feng1, Jie Zhu4, Mingqin Zhu5. 1. Department of Neurology, The First Hospital of Jilin University, Xinmin Street 71#, Changchun 130021, China. 2. Department of Neurobiology, Care Sciences & Society, Section of Neurodegeneration, Karolinska Institute, Center for Alzheimer Research, Blickagången 6, SE-141 57 Huddinge, Sweden. 3. Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. 4. Department of Neurology, The First Hospital of Jilin University, Xinmin Street 71#, Changchun 130021, China; Department of Neurobiology, Care Sciences & Society, Section of Neurodegeneration, Karolinska Institute, Center for Alzheimer Research, Blickagången 6, SE-141 57 Huddinge, Sweden. 5. Department of Neurology, The First Hospital of Jilin University, Xinmin Street 71#, Changchun 130021, China. Electronic address: mingqin.zhu@hotmail.com.
Abstract
BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are a spectrum of neuroinflammatory disorders associated with autoimmune antibodies against aquaporin-4 (AQP4). Accumulating evidence suggests that inflammation is involved in NMOSD pathogenesis. Resolution of inflammation, which is a highly regulated process mediated by specialized pro-resolving lipid mediators (SPMs) is important to prevent over-responsive inflammation. Deficiency in resolution of inflammation may lead to or accelerates inflammatory diseases. However, whether resolution of inflammation is impaired in NMOSD is not known. The objective of this study was to analyze the levels of SPMs in the serum and cerebrospinal fluid (CSF) of NMOSD patients, and to explore the roles of SPMs in clinical features of NMOSD. METHODS: Thirty-five patients with NMOSD, 34 patients with multiple sclerosis, and 36 patients with non-inflammatory neurological diseases were enrolled in this study. Pro-resolving mediators including Annexin A1 (ANXA1) and resolvin D1 (RvD1), as well as pro-inflammatory lipid mediator leukotriene B4 (LTB4) levels were analyzed by enzyme-linked immunosorbent assay. Pro- and anti-inflammatory cytokines as well as chemokine levels were analyzed using cytometric beads array (CBA). RESULTS: Our results showed RvD1 levels were significantly decreased, whereas LTB4 levels were significantly increased in the CSF of NMOSD patients. AQP4-IgG titer was negatively correlated with RvD1 levels in the CSF of NMOSD patients. CONCLUSIONS: Decreased RvD1 levels indicate impaired resolution of inflammation in NMOSD patients. AQP4-IgG may contribute to increased inflammation and lead to unresolved inflammation in NMOSD.
BACKGROUND:Neuromyelitis optica spectrum disorders (NMOSD) are a spectrum of neuroinflammatory disorders associated with autoimmune antibodies against aquaporin-4 (AQP4). Accumulating evidence suggests that inflammation is involved in NMOSD pathogenesis. Resolution of inflammation, which is a highly regulated process mediated by specialized pro-resolving lipid mediators (SPMs) is important to prevent over-responsive inflammation. Deficiency in resolution of inflammation may lead to or accelerates inflammatory diseases. However, whether resolution of inflammation is impaired in NMOSD is not known. The objective of this study was to analyze the levels of SPMs in the serum and cerebrospinal fluid (CSF) of NMOSD patients, and to explore the roles of SPMs in clinical features of NMOSD. METHODS: Thirty-five patients with NMOSD, 34 patients with multiple sclerosis, and 36 patients with non-inflammatory neurological diseases were enrolled in this study. Pro-resolving mediators including Annexin A1 (ANXA1) and resolvin D1 (RvD1), as well as pro-inflammatory lipid mediator leukotriene B4 (LTB4) levels were analyzed by enzyme-linked immunosorbent assay. Pro- and anti-inflammatory cytokines as well as chemokine levels were analyzed using cytometric beads array (CBA). RESULTS: Our results showed RvD1 levels were significantly decreased, whereas LTB4 levels were significantly increased in the CSF of NMOSD patients. AQP4-IgG titer was negatively correlated with RvD1 levels in the CSF of NMOSD patients. CONCLUSIONS: Decreased RvD1 levels indicate impaired resolution of inflammation in NMOSD patients. AQP4-IgG may contribute to increased inflammation and lead to unresolved inflammation in NMOSD.
Authors: Ana Paula Bornes da Silva; Rodrigo Braccini Madeira Silva; Leise Daniele Sckenal Goi; Rachel Dias Molina; Denise Cantarelli Machado; Douglas Kazutoshi Sato Journal: Front Neurol Date: 2020-05-12 Impact factor: 4.003
Authors: Maria Consiglia Trotta; Sami Gharbia; Hildegard Herman; Bianca Mladin; Andrei Hermenean; Cornel Balta; Coralia Cotoraci; Victor Eduard Peteu; Carlo Gesualdo; Francesco Petrillo; Marilena Galdiero; Roberto Alfano; Mihaela Gherghiceanu; Michele D'Amico; Settimio Rossi; Anca Hermenean Journal: Int J Mol Sci Date: 2021-06-11 Impact factor: 5.923