2022
Cell-Free DNA Derived From Neutrophils Triggers Type 1 Interferon Signature in Neuromyelitis Optica Spectrum Disorder
Murata H, Kinoshita M, Yasumizu Y, Motooka D, Beppu S, Shiraishi N, Sugiyama Y, Kihara K, Tada S, Koda T, Konaka H, Takamatsu H, Kumanogoh A, Okuno T, Mochizuki H. Cell-Free DNA Derived From Neutrophils Triggers Type 1 Interferon Signature in Neuromyelitis Optica Spectrum Disorder. Neurology Neuroimmunology & Neuroinflammation 2022, 9: e1149. PMID: 35210295, PMCID: PMC8874356, DOI: 10.1212/nxi.0000000000001149.Peer-Reviewed Original ResearchMeSH KeywordsCell-Free Nucleic AcidsHumansInterferonsLeukocytes, MononuclearNeuromyelitis OpticaNeutrophilsConceptsNeuromyelitis optica spectrum disorderPeripheral blood mononuclear cellsCell-free DNAAquaporin-4 antibody-positive neuromyelitis optica spectrum disorderAntibody-positive neuromyelitis optica spectrum disorderPathogenesis of neuromyelitis optica spectrum disordersToll-like receptor 9 antagonistIFN-1IFN-1 pathwayInhibition of NETosisPeripheral immune systemOrigin of cell-free DNABlood mononuclear cellsPredominant cellular sourceIFN-1 productionType 1 interferonLL37 antimicrobial peptideWhole blood transcriptome analysisAquaporin-4Mononuclear cellsCfDNA fractionDNA methylation profilesBlood transcriptome analysisHealthy subjectsCellular sourceHigh cell surface expression and peptide binding affinity of HLA-DQA1*05:03, a susceptible allele of neuromyelitis optica spectrum disorders (NMOSD)
Beppu S, Kinoshita M, Wilamowski J, Suenaga T, Yasumizu Y, Ogawa K, Ishikura T, Tada S, Koda T, Murata H, Shiraishi N, Sugiyama Y, Kihara K, Sugimoto T, Arase H, Standley D, Okuno T, Mochizuki H. High cell surface expression and peptide binding affinity of HLA-DQA1*05:03, a susceptible allele of neuromyelitis optica spectrum disorders (NMOSD). Scientific Reports 2022, 12: 106. PMID: 34997058, PMCID: PMC8742014, DOI: 10.1038/s41598-021-04074-1.Peer-Reviewed Original ResearchConceptsNeuromyelitis optica spectrum disorderPeptide major histocompatibility complexDevelopment of neuromyelitis optica spectrum disorderAnti-aquaporin-4HLA-DQA1Associated with neuromyelitis optica spectrum disordersHigh cell surface expressionJapanese patient cohortPresence of pathogenic autoantibodiesCell surface expression levelsRelapsing autoimmune diseaseHLA-DQA1 allelesCell surface expressionSurface expression levelsAQP4 peptidesMajor histocompatibility complexAnti-aquaporinPathogenic autoantibodiesHLA-DQPatient cohortAutoimmune diseasesPathogenic roleSurface expressionIn silico 3D structure modelingHistocompatibility complex
2021
Anti-AQP4 autoantibodies promote ATP release from astrocytes and induce mechanical pain in rats
Ishikura T, Kinoshita M, Shimizu M, Yasumizu Y, Motooka D, Okuzaki D, Yamashita K, Murata H, Beppu S, Koda T, Tada S, Shiraishi N, Sugiyama Y, Miyamoto K, Kusunoki S, Sugimoto T, Kumanogoh A, Okuno T, Mochizuki H. Anti-AQP4 autoantibodies promote ATP release from astrocytes and induce mechanical pain in rats. Journal Of Neuroinflammation 2021, 18: 181. PMID: 34419102, PMCID: PMC8380350, DOI: 10.1186/s12974-021-02232-w.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsAquaporin 4AstrocytesAutoantibodiesHEK293 CellsHumansNeuralgiaNeuromyelitis OpticaRatsConceptsNeuromyelitis optica spectrum disorderIgG-treated ratsMechanical allodyniaNeuropathic painSpinal cordATP receptorsATP releaseSymptoms of neuromyelitis optica spectrum disorderDevelopment of mechanical allodyniaDevelopment of neuropathic painPharmacological inhibitionDevelopment of painful symptomsAnti-AQP4 autoantibodiesPeripheral neuropathic painAnti-AQP4 antibodyRelease of extracellular ATPExtracellular ATP releaseRat spinal cordDamage-associated molecular patternsAnti-AQP4Pain mechanismsMechanical painInvolvement of ATPPain symptomsRemission phase