title: Seroprevalence of aquaporin-4-IgG in a northern California population representative cohort of multiple sclerosis.
abstract: OBJECTIVE
  Using an aquaporin-4 (AQP4) M1-isoform-specific enzyme-linked immunosorbent assay (ELISA) and a fixed transfected cell-based assay (CBA), we tested AQP4-IgG in a northern California population representative cohort of 3293 potential cases with multiple sclerosis (MS). Seropositive cases were tested additionally by fluorescence-activated cell sorting, a live transfected cell-based assay.
  
  
  METHODS
  Sera samples were available in 1040 cases; 7 yielded positive results, 4 by ELISA alone and 3 by both ELISA and CBA. Clinical data (episodes of optic neuritis and longitudinally extensive transverse myelitis [reported on at least 1 magnetic resonance imaging spine]) supported the alternative diagnosis of neuromyelitis optica for 2 patients as seropositive by both ELISA and CBA. These 2 patients alone tested positive by a fluorescence-activated cell-sorting assay. The diagnosis of MS was considered correct in the other 5 patients. Thus, 5 ELISA results and 1 fixed CBA result were false positive.
  
  
  CONCLUSIONS
  Sensitive serological evaluation for AQP4-IgG in this large population-representative cohort of predominantly white non-Hispanic patients with MS reveals that neuromyelitis optica spectrum disorder is rarely misdiagnosed as MS in contemporary US neurological practice (0.2%). The frequency of a false-positive result for ELISA and CBA in this MS cohort were 0.5% and 0.1%, respectively. This finding reflects the superior specificity of CBA and justifies caution in interpreting AQP4-IgG results obtained by ELISA.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota2Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Pittock
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota2Department of Neurology, Mayo Clinic, Rochester, Minnesota3Department of Immunology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Vanda A
authors.initials: VA
authors.lastname: Lennon
authors.affiliation: The Permanente Medical Group, Oakland, California.
authors.forename: Nandini
authors.initials: N
authors.lastname: Bakshi
authors.affiliation: Kaiser Permanente Division of Research, Oakland, California.
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota2Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Andrew
authors.initials: A
authors.lastname: McKeon
authors.affiliation: Genetic Epidemiology and Genomics Laboratory, Division of Epidemiology, School of Public Health, University of California, Berkeley.
authors.forename: Hong
authors.initials: H
authors.lastname: Quach
authors.affiliation: Genetic Epidemiology and Genomics Laboratory, Division of Epidemiology, School of Public Health, University of California, Berkeley.
authors.forename: Farren B S
authors.initials: FB
authors.lastname: Briggs
authors.affiliation: Palm Drive Hospital, Sebastopol, California.
authors.forename: Allan L
authors.initials: AL
authors.lastname: Bernstein
authors.affiliation: Kaiser Permanente Division of Research, Oakland, California.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Schaefer
authors.affiliation: Kaiser Permanente Division of Research, Oakland, California6Genetic Epidemiology and Genomics Laboratory, Division of Epidemiology, School of Public Health, University of California, Berkeley.
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
mesh_terms: D000328:Adult; D000368:Aged; D051401:Aquaporin 4 / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D002140:California; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000276:immunology; D009188:Myelitis, Transverse / Q000097:blood / Q000175:diagnosis; D009902:Optic Neuritis / Q000175:diagnosis / Q000276:immunology; D016036:Seroepidemiologic Studies
chemical_list: D051401:Aquaporin 4; D001323:Autoantibodies; D007074:Immunoglobulin G