title: Characterization of a new highly sensitive immunometric assay for thyroglobulin with reduced interference from autoantibodies.
abstract: Measurements of serum thyroglobulin (Tg) with sensitive immunoassays are of great importance for the management of patients with differentiated thyroid carcinomas. However, interference of circulating autoantibodies to Tg (hTgAb) hampers the usefulness of most assays. We have produced a panel of monoclonal antibodies (mAbs) selected to bind Tg in the presence of Tg autoantibodies and developed a sensitive immunoassay for Tg with minor interference by hTgAbs. The antibodies were characterized by cross-inhibition and immunoassay combination studies, as well as affinity estimation. The within-run and total imprecision of the assay were determined with 2664 samples in 60 separate runs. The most sensitive assay combination with superior protection against autoantibodies consisted of two solid phase mAbs and two tracer mAbs with distinct binding sites. The assay was linear and displayed a wide dynamic range up to 1342 μg/l with a functional sensitivity of 0.1 μg/l and a total imprecision of less than 10 %. There was good agreement between the new high sensitive immunofluorometric assay (IFMA) and two well-established Tg assays from Brahms Kryptor and Roche Diagnostics. Mean difference between the new IFMA and the Kryptor assay was 0.059 μg/l with a 95 % confidence interval of -0.032 to 0.151 μg/l, whereas the mean difference between the new IFMA and the Roche assay was -0.80 μg/l with a 95 % confidence interval of -1.24 to -0.35 μg/l.
authors.affiliation: Department of Medical Biochemistry, Radiumhospitalet, Oslo University Hospital (OUH), Oslo, Norway. mnordl@ous-hf.no.
authors.forename: Marianne Nordlund
authors.initials: MN
authors.lastname: Broughton
authors.affiliation: Department of Medical Biochemistry, Radiumhospitalet, Oslo University Hospital (OUH), Oslo, Norway.
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Nome
authors.affiliation: Department of Medical Biochemistry, Radiumhospitalet, Oslo University Hospital (OUH), Oslo, Norway.
authors.forename: Ingvill
authors.initials: I
authors.lastname: Sandven
authors.affiliation: Department of Medical Biochemistry, Radiumhospitalet, Oslo University Hospital (OUH), Oslo, Norway.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Paus
authors.affiliation: Department of Medical Biochemistry, Radiumhospitalet, Oslo University Hospital (OUH), Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Trine
authors.initials: T
authors.lastname: Bjøro
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000097:blood* / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D000937:Antigen-Antibody Reactions; D016477:Artifacts; D001323:Autoantibodies / Q000276:immunology; D002291:Carcinoma, Papillary / Q000097:blood* / Q000276:immunology; D018604:Epitope Mapping; D005260:Female; D015200:Fluoroimmunoassay / Q000379:methods*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D012680:Sensitivity and Specificity; D013954:Thyroglobulin / Q000097:blood* / Q000276:immunology; D013964:Thyroid Neoplasms / Q000097:blood* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; C006606:anti-thyroglobulin; D013954:Thyroglobulin
keywords: Autoantibodies; Immunoassay; Thyroglobulin; Thyroid carcinoma; Time-resolved