A novel cell-based assay for measuring neutralizing autoantibodies against type I interferons in patients with autoimmune polyendocrine syndrome type 1

• Published in: Clinical immunology (Orlando, Fla.) Vol. 153; no. 1; pp. 220 - 227
• Main Authors: Breivik, Lars, Oftedal, Bergithe E.V, Bøe Wolff, Anette S, Bratland, Eirik, Orlova, Elizaveta M, Husebye, Eystein S
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2014
• Subjects: Allergy and Immunology; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Autoantibodies - blood; Autoantibodies - immunology; Autoimmune polyendocrine syndrome I; Cell Line; Humans; Immunoassay - methods; Interferon alpha; Interferon omega; Interferon Type I - antagonists & inhibitors; Interferon Type I - immunology; Neutralizing autoantibodies; Polyendocrinopathies, Autoimmune - blood; Polyendocrinopathies, Autoimmune - immunology; Radioimmunoassay; Sensitivity and Specificity; Neutralizing autoantibodies; Autoimmune polyendocrine syndrome I; Radioimmunoassay; Interferon omega; Interferon alpha
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2014.04.013

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.