Iodine contributes to thyroid autoimmunity in humans by unmasking a cryptic epitope on thyroglobulin

J Clin Endocrinol Metab. 2013 Nov;98(11):E1768-74. doi: 10.1210/jc.2013-2912. Epub 2013 Sep 24.

Abstract

Context: 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.

Setting: The general community living in an Italian village was evaluated.

Main outcome measures: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / immunology
  • Autoantibodies / blood
  • Epitopes / immunology*
  • Female
  • Hashimoto Disease / diagnostic imaging
  • Hashimoto Disease / diet therapy
  • Hashimoto Disease / immunology*
  • Humans
  • Hypothyroidism / diagnostic imaging
  • Hypothyroidism / diet therapy
  • Hypothyroidism / immunology*
  • Iodide Peroxidase / immunology
  • Iodine / administration & dosage*
  • Iodine / urine
  • Italy
  • Male
  • Middle Aged
  • Sodium Chloride, Dietary / administration & dosage*
  • Sodium Chloride, Dietary / urine
  • Thyroglobulin / immunology*
  • Thyroiditis, Autoimmune / diagnostic imaging
  • Thyroiditis, Autoimmune / diet therapy
  • Thyroiditis, Autoimmune / immunology*
  • Ultrasonography

Substances

  • Antibodies, Monoclonal
  • Autoantibodies
  • Epitopes
  • Sodium Chloride, Dietary
  • iodized salt
  • Thyroglobulin
  • Iodine
  • Iodide Peroxidase