Iodine contributes to thyroid autoimmunity in humans by unmasking a cryptic epitope on thyroglobulin.
BACKGROUND
The mechanisms linking thyroid autoimmunity and iodine use in humans are unknown.


OBJECTIVE
Our aim was to correlate iodine intake, thyroid autoimmunity, and recognition of thyroglobulin (Tg) epitopes after implementation of iodine prophylaxis.


METHODS
The general community living in an Italian village was evaluated.


METHODS
Thyroglobulin autoantibodies (TgAb), thyroperoxidase autoantibodies (TPOAb), and urinary iodine excretion were assessed in 906 iodized salt users (IS-users) and 389 nonusers (IS-nonusers). Ultrasound (US) was performed to identify thyroid hypoechogenicity, suggestive of Hashimoto thyroiditis (HT). TgAb epitope pattern in 16 IS-users and 17 IS-nonusers was evaluated by an inhibition binding assay to Tg, using human monoclonal TgAb-Fab directed to A, B, C, and D epitopes on Tg.


RESULTS
Median urinary iodine excretion was slightly higher in IS-users than in IS-nonusers (112.0 μg/L vs 86.5 μg/L; P < .01). TgAb, and not TPOAb, was more frequent in IS-users (18.9% vs 13.6%, P = .02). HT-US was found in 87 subjects, among whom both positive TgAb (58.4% vs 31.8%, P = .03) and TPOAb (61.5% vs 45.4%. P = .04) were more frequent in IS-users. In this group significantly higher serum levels of TgAb (median 108 U/mL vs 30 U/mL; P = .02), but not of TPOAb, were present. Iodized salt use had no effect on the 1208 non HT-US subjects. TgAb directed to the epitope B of Tg were more frequent in IS-users than in IS-nonusers (27.5% vs 3.0%, P = .047).


CONCLUSIONS
Iodine-induced thyroid autoimmunity is related to TgAb and the unmasking of a cryptic epitope on Tg contributes to this relationship in humans.
Endocrinology Unit, University Hospital, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy. paolo.vitti@med.unipi.it.
Francesco
F
Latrofa
Emilio
E
Fiore
Teresa
T
Rago
Lucia
L
Antonangeli
Lucia
L
Montanelli
Debora
D
Ricci
Maria Annateresa
MA
Provenzale
Maria
M
Scutari
Monica
M
Frigeri
Massimo
M
Tonacchera
Paolo
P
Vitti
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D000939:Epitopes / Q000276:immunology*; D005260:Female; D050031:Hashimoto Disease / Q000000981:diagnostic imaging / Q000178:diet therapy / Q000276:immunology*; D006801:Humans; D007037:Hypothyroidism / Q000000981:diagnostic imaging / Q000178:diet therapy / Q000276:immunology*; D007453:Iodide Peroxidase / Q000276:immunology; D007455:Iodine / Q000008:administration & dosage* / Q000652:urine; D007558:Italy; D008297:Male; D008875:Middle Aged; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000652:urine; D013954:Thyroglobulin / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000000981:diagnostic imaging / Q000178:diet therapy / Q000276:immunology*; D014463:Ultrasonography
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D017673:Sodium Chloride, Dietary; C034024:iodized salt; D013954:Thyroglobulin; D007455:Iodine; D007453:Iodide Peroxidase