Thyroglobulin antibodies (TgAbs) are typically found in autoimmune thy
roid diseases and, more rarely, in nonautoimmune thyroid diseases and
healthy subjects. To determine whether TgAbs associated with different
conditions recognize different epitopes on the thyroglobulin molecule
, we studied 28 patients with Hashimoto's thyroiditis, 30 with Graves'
disease, 21 with thyroid carcinoma, 18 with nontoxic goiter, and 2 5
healthy subjects. All patients were selected for the presence of TgAbs
; 4/25 healthy subjects also had TpAbs. The sera were assayed for the
their ability to inhibit the binding of monoclonal antibodies to thyro
globulin in an ELISA assay. We found that: 1) TgAbs in Hashimoto's pat
ients preferentially recognized three clusters of epitopes (II, III an
d typically VI), with no difference between the goitrous and the atrop
hic variants; 2) TgAbs in Graves' patients were directed toward cluste
r II, with no difference between the presence or the absence of ophtha
lmopathy; 3) TgAbs in thyroid carcinoma patients recognized the same c
lusters as Hashimoto's patients; 4) TgAbs in nontoxic goiter patients
and in the four healthy subjects showed no restriction in epitope reco
gnition. We suggest that in individuals with no overt clinical or bioc
hemical thyroid abnormalities but with TgAbs, the finding that these T
gAbs recognize particular immunodominant clusters may be utilized to p
redict full-blown thyroid disorders. Longitudinal studies are needed t
o evaluate the possible clinical application of this methodology.