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This version published online on November 20, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-1199
A more recent version of this article appeared on February 1, 2008
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Right arrow Thyroid
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Submitted on June 22, 2007
Accepted on November 9, 2007

Characterization of thyroglobulin epitopes in patients with autoimmune and non-autoimmune thyroid diseases using recombinant human monoclonal thyroglobulin autoantibodies

Francesco Latrofa*, Debora Ricci, Lucia Grasso, Paolo Vitti, Lucio Masserini, Fulvio Basolo, Clara Ugolini, Giovanni Mascia, Antonio Lucacchini, and Aldo Pinchera

Department of Endocrinology, WHO collaborating Center for the Diagnosis and Treatment of Thyroid Cancer and Other Thyroid Diseases (F.L., D.R., L.G., P.V., A.P.), Department of Statistic and Economy (L.M.), Department of Oncology, Section of Pathology 3 (F.B., C.U.), Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology (G.M., A.L.), University of Pisa, Italy

* To whom correspondence should be addressed. E-mail: latrofaf{at}libero.it.

Context: Thyroglobulin (Tg) epitopes of serum Tg autoantibodies (TgAb) have been characterized using inhibition of Tg binding by human monoclonal TgAb in autoimmune thyroid diseases (AITD) (Hashimoto's thyroiditis, HT, and Graves' disease, GD) but not in non-autoimmune thyroid diseases (non-AITD) (non toxic multinodular goiter, NTMG, and papillary thyroid carcinoma, PTC).

Objective: To compare Tg epitopes of serum TgAb from patients with AITD, non-AITD and PTC associated with histological thyroiditis (PTC-T) using inhibition of Tg binding by 4 recombinant human TgAb-Fab (epitopic regions A to D).

Design: Inhibition of Tg binding of 24 HT, 25 GD, 19 NTMG, 15 PTC and 25 PTC-T TgAb positive sera by each TgAb-Fab was evaluated in ELISA. Inhibition by the pool of the 4 TgAb-Fab was evaluated using labeled Tg.

Results: Levels of inhibition were different for TgAb-Fab regions A (p =0.001), B (0.007) and D (0.011). Inhibition by region A TgAb-Fab was significantly higher in HT, GD and PTC-T than in NTMG and PTC patients. Inhibition levels by region B TgAb-Fab were significantly higher in HT compared with NTMG and PTC patients and in GD compared with NTMG patients. Inhibition by D region TgAb-Fab was significantly lower in NTMG than in the other groups. Inhibition by the pool ranged from 44% (NTMG) to 72% (GD).

Conclusions: The pattern of Tg recognition is similar when HT are compared to GD and NTMG to PTC patients and differs when AITD are compared with non-AITD patients. In PTC-T patients it is similar to that of AITD patients.
Key words: thyroglobulin epitopes • thyroglobulin autoantibodies • recombinant human monoclonal autoantibodies • autoimmune thyroid diseases • non-autoimmune thyroid diseases






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