Characterization of thyroglobulin epitopes in patients with autoimmune and non-autoimmune thyroid diseases using recombinant human monoclonal thyroglobulin autoantibodies.
BACKGROUND
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-AITD [nontoxic multinodular goiter (NTMG) and papillary thyroid carcinoma (PTC)].


OBJECTIVE
Our objective was 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 four recombinant human TgAb-Fab (epitopic regions A-D).


METHODS
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 four 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 patients 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.
Latrofa
Francesco
F
Department of Endocrinology, University Hospital of Pisa, Via Cisanello 2, 56124 Pisa, Italy. latrofaf@libero.it
Ricci
Debora
D
Grasso
Lucia
L
Vitti
Paolo
P
Masserini
Lucio
L
Basolo
Fulvio
F
Ugolini
Clara
C
Mascia
Giovanni
G
Lucacchini
Antonio
A
Pinchera
Aldo
A
D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001667:Binding, Competitive / Q000276:immunology; D002291:Carcinoma, Papillary / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes / Q000032:analysis; D006044:Goiter, Nodular / Q000276:immunology*; D006111:Graves Disease / Q000276:immunology*; D050031:Hashimoto Disease / Q000276:immunology*; D006801:Humans; D011994:Recombinant Proteins; D013954:Thyroglobulin / Q000276:immunology*; D013964:Thyroid Neoplasms / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D011994:Recombinant Proteins; D013954:Thyroglobulin