title: Large-Scale in-House Cell-Based Assay for Evaluating the Serostatus in Patients with Neuromyelitis Optica Spectrum Disorder Based on New Diagnostic Criteria.
abstract: OBJECTIVE
  The detection of aquaporin 4-IgG (AQP4-IgG) is now a critical diagnostic criterion for neuromyelitis optica spectrum disorder (NMOSD). To evaluate the serostatus of NMOSD patients based on the 2015 new diagnostic criteria using a new in-house cell-based assay (CBA).
  
  
  METHODS
  We generated a stable cell line using internal ribosome entry site-containing bicistronic vectors, which allow the simultaneous expression of two proteins (AQP4 and green fluorescent protein) separately from the same RNA transcript. We performed in-house CBA using serum from 386 patients: 178 NMOSD patients diagnosed according to the new diagnostic criteria without AQP4-IgG, 63 high risk NMOSD patients presenting 1 of the 6 core clinical characteristics of NMOSD but not fulfilling dissemination in space, and 145 patients with other neurological diseases, including 66 with multiple sclerosis. The serostatus of 111 definite and high risk NMOSD patients were also tested using a commercial CBA kit with identical serum to evaluate the correlation between the 2 methods. All assays were performed by two independent and blinded investigators.
  
  
  RESULTS
  Our in-house assay yielded a specificity of 100% and sensitivities of 80% (142 of 178) and 76% (48 of 63) when detecting definite- and high risk NMOSD patients, respectively. The comparison with the commercial CBA kit revealed a correlation for 102 of the 111 patients: no correlation was present in 7 patients who were seronegative using the commercial method but seropositive using the in-house method, and in 2 patients who were seropositive using the commercial method but seronegative using the in-house method.
  
  
  CONCLUSIONS
  These results demonstrate that our in-house CBA is a highly specific and sensitive method for detecting AQP4-IgG in NMOSD patients.
authors.affiliation: Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.|Division of Translational and Clinical Research II, Research institute, National Cancer Center, Goyang, Korea.
authors.forename: Yeseul
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.|Division of Translational and Clinical Research II, Research institute, National Cancer Center, Goyang, Korea.
authors.forename: Gayoung
authors.initials: G
authors.lastname: Kim
authors.affiliation: Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.|Division of Translational and Clinical Research II, Research institute, National Cancer Center, Goyang, Korea.
authors.forename: Byung Soo
authors.initials: BS
authors.lastname: Kong
authors.affiliation: Division of Translational and Clinical Research II, Research institute, National Cancer Center, Goyang, Korea.|Department of Biochemistry and Molecular Biology, and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Division of Translational and Clinical Research II, Research institute, National Cancer Center, Goyang, Korea.|Department of Biochemistry and Molecular Biology, and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Oh
authors.affiliation: Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Hyun
authors.affiliation: Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
authors.forename: Su Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
authors.forename: AeRan
authors.initials: A
authors.lastname: Joung
authors.affiliation: Department of Neurology, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Byoung Joon
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kyungho
authors.initials: K
authors.lastname: Choi
authors.affiliation: Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.|Division of Translational and Clinical Research II, Research institute, National Cancer Center, Goyang, Korea. hojinkim@ncc.re.kr.
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Kim
keywords: aquaporin 4; aquaporin 4-IgG; cell-based immunofluorescence assay; neuromyelitis optica spectrum disorder