title: A novel cell-based assay for measuring neutralizing autoantibodies against type I interferons in patients with autoimmune polyendocrine syndrome type 1.
abstract: An important characteristic of autoimmune polyendocrine syndrome type 1 (APS 1) is the existence of neutralizing autoantibodies (nAbs) against the type I interferons (IFN) -α2 and -ω at frequencies close to 100%. Type 1 IFN autoantibodies are detected by antiviral neutralizing assays (AVA), binding assays with radiolabelled antigens (RLBA), enzyme-linked immunosorbent assay (ELISA), or by reporter-based cell assays. We here present a simple and reliable version of the latter utilizing a commercially available cell line (HEK-Blue IFN-α/β). All 67 APS 1 patients were positive for IFN-ω nAbs, while 90% were positive for IFN-α2 nAbs, a 100% and 96% correlation with RLBA, respectively. All blood donors and non-APS 1 patients were negative. The dilution titer required to reduce the effect of IFN-ω nAbs correlated with the RLBA index. This cell-based autoantibody assay (CBAA) is easy to perform, suitable for high throughput, while providing high specificity and sensitivity.
authors.affiliation: Section for Endocrinology, Department of Clinical Science, University of Bergen, N-5020 Bergen, Norway. Electronic address: lars.breivik@k2.uib.no.
authors.forename: Lars
authors.initials: L
authors.lastname: Breivik
authors.affiliation: Section for Endocrinology, Department of Clinical Science, University of Bergen, N-5020 Bergen, Norway.
authors.forename: Bergithe E V
authors.initials: BE
authors.lastname: Oftedal
authors.affiliation: Section for Endocrinology, Department of Clinical Science, University of Bergen, N-5020 Bergen, Norway.
authors.forename: Anette S
authors.initials: AS
authors.lastname: Bøe Wolff
authors.affiliation: Section for Endocrinology, Department of Clinical Science, University of Bergen, N-5020 Bergen, Norway.
authors.forename: Eirik
authors.initials: E
authors.lastname: Bratland
authors.affiliation: Endocrinological Research Centre, Institute of Paediatric Endocrinology, Moscow, 117036, Russia.
authors.forename: Elizaveta M
authors.initials: EM
authors.lastname: Orlova
authors.affiliation: Section for Endocrinology, Department of Clinical Science, University of Bergen, N-5020 Bergen, Norway; Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway.
authors.forename: Eystein S
authors.initials: ES
authors.lastname: Husebye
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002460:Cell Line; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007370:Interferon Type I / Q000037:antagonists & inhibitors* / Q000276:immunology*; D016884:Polyendocrinopathies, Autoimmune / Q000097:blood* / Q000276:immunology*; D012680:Sensitivity and Specificity
chemical_list: D057134:Antibodies, Neutralizing; D001323:Autoantibodies; D007370:Interferon Type I
keywords: Autoimmune polyendocrine syndrome I; Interferon alpha; Interferon omega; Neutralizing autoantibodies; Radioimmunoassay