Thyroglobulin Antibodies in Serum of Patients with Differentiated Thyroid Cancer: Relationship between Epitope Specificities and Thyroglobulin Recovery

Abstract

Background: Serum antibodies against thyroglobulin (TgAbs) are common in patients with differentiated thyroid cancer (DTC) and can interfere in thyroglobulin (Tg) assays. We identified the epitopes on Tg recognized by TgAb-positive sera from patients with DTC and examined the association between epitope specificity patterns and Tg recovery. Methods: We tested 50 DTC sera for Tg epitope specificity, TgAbs, and Tg recovery. Epitope recognition was determined by use of a panel of 10 well-characterized Tg monoclonal antibodies directed against 6 Tg antigenic clusters (I-VI) in competitive reactions with test sera. Tg was measured by the Thyroglobuline IRMA (CIS bio international). Recovery of added Tg (TgREC) was determined by an in-house assay. Results: Epitope recognition was restricted to immunodominant clusters in 58% of patients, whereas the rest were either broadly heterogeneous (16%) or nonreactive (26%). Median Tg recovery did not differ between sera with restricted and unrestricted specificities (69% vs 80%; P >0.05). TgREC was inversely correlated with the total number of epitopes recognized by sera (r ‫؍‬ ؊0.66; P <0.001). Conclusions: TgAbs with both restricted and broad specificities are present in patients with DTC. TgAb

Comparaison entre les tests de surcharge et le dosage radio-immunologique des anticorps antithyroglobuline pour la validation des dosages de la thyroglobuline

“…Cependant, considérer qu'un dosage de thyroglobuline n'est pas fiable en présence d'anticorps dé-celables, revient à priver environ 20 % des patients de la surveillance de leur cancer thyroïdien par un marqueur qui a fait la preuve de son efficacité clinique, alors qu'il est clair qu'aucune technique de dosage d'anticorps ne peut renseigner valablement sur le niveau exact d'interférence que peuvent avoir ces autoanticorps antithyroglobuline dans le dosage de la thyroglobuline chez un patient donné [23][24][25]. Une étude récente d'Okosieme montre que l'interférence due aux autoanticorps antithyroglobuline serait plus liée au nombre total d'épitopes différents reconnus qu'aux caractéristiques de ces épitopes [16]. L'étude multicentrique récente rapportée par Spencer [26] suggère que les anciennes méthodes radio-immunologiques de dosages de la thyroglobuline utilisant des anticorps polyclonaux semblent être celles qui sont les moins sensibles aux interférences liées à la présence d'anticorps antithyroglobuline.…”

Measuring Thyroglobulin Concentrations in Patients with Differentiated Thyroid Carcinoma

“…The principle of RIA tests is competitive binding by polyclonal antibodies, which have greater possibilities of recognizing epitopes exposed on Tg molecules bound to TgAb (9,(11)(12)(13). The method of disrupting binding of the TgAb-Tg complex to antibody in IMA tests could be twofold: stearic inhibition or masking of the epitope that recognizes the monoclonal antibody in the diagnostic kit, but there are no experimental data for this mechanistic concept (9,11,66).…”

“…Epitope mapping on the Tg molecule has shown the existence of six different antigenic regions to which different thyroglobulin-specific antibodies (TgAb) can bind (9, 10), most probably due to differences in Tg molecules secreted from malignantly changed thyroid cells (9,(11)(12)(13).…”

Detection of thyroglobulin in antithyroglobulin antibody-positive sera by isoelectric focusing

“…False positive or negative results in Tg concentrations due to the presence of interfering antibodies or by other factors still seem to be a major problem [1][2][3].…”