Characterization of thyroglobulin epitopes in Sardinian adults and juveniles with Hashimoto's thyroiditis: evidence against a major effect of age and genetic background on B-cell epitopes.

Abstract

Background Using recombinant human monoclonal thyroglobulin antibodies expressed as Fab molecules (TgAb-Fab), we have recently confirmed the restriction of Tg epitopes in Hashimoto’s thyroiditis (HT). Objective To investigate Tg epitopes of serum TgAb in HT adults and HT juveniles from a geographically isolated area (Sardinia). Design and Patients Serum TgAb of 39 Sardinian HT adults, 53 Sardinian HT juveniles and 45 non-Sardinian HT adults were evaluated. The binding of serum TgAb to Tg in ELISA was inhibited by four recombinant human TgAb-Fab, identifying Tg epitopic regions A–D. The percentage of Tg binding inhibition was calculated comparing the binding of serum TgAb in presence of each TgAb-Fab with that in its absence. Results In the whole cohort of 137 patients, A region TgAb-Fab induced the highest levels of inhibition (55Æ3 ± 17Æ8%) (mean ± SD). Lower levels of inhibition were induced by TgAb- Fab of regions B (27Æ8 ± 25Æ8%), C (26Æ8 ± 24Æ6%) and D (17Æ5 ± 18Æ4%). In Sardinian HT adults inhibition by TgAb-Fab of regions A, B and C were comparable to Sardinian HT juveniles; the marginal D region TgAb-Fab induced a slightly higher inhibition (22Æ1 vs. 13Æ8%; P = 0Æ034) in the former than in the latter group. In Sardinian and non-Sardinian HT adults inhibitions by the four TgAb-Fab were similar. Conclusions In HT, the Tg epitope pattern of serum TgAb was similar in juveniles and adults from a geographically restricted area and in two adult populations from different geographical areas. Thus, in HT, neither age nor genetic background appear to influence B-cell epitopes