The incorporation of dietary iodine into thyroglobulin increases its immunogenicity.

Experiments were performed to analyze one mechanism by which elevated levels of dietary iodine may induce thyroglobulin (Tg) autoantibodies. We tested the hypothesis that highly iodinated Tg synthesized by animals fed a high iodine diet is significantly more immunogenic than Tg containing fewer iodine atoms. Cornell strain (CS) chickens, genetically susceptible to iodide-induced thyroiditis, were fed either a high or a low iodine diet. They were killed, and their thyroidal Tg was analyzed for iodine; the high iodine Tg (HI-Tg) had at least 60 and the low iodine Tg (LI-Tg) had less than 13 atoms/molecule of Tg. To determine if the degree of Tg iodination affected its immunogenicity, these Tg preparations were administered iv to normal chickens without adjuvants. Their sera were tested for antibodies by direct binding radioassays and RIAs. HI-Tg stimulated the synthesis of antibodies that reacted well with HI-Tg and the thyroid hormones T3 and T4, but only weakly with LI-Tg. The birds immunized with LI-Tg produced very little antibody to LI-Tg, T3, or T4, but a modest amount to HI-Tg. In other experiments, Tg autoantibodies found in chickens maintained on a high iodine diet similarly demonstrated enhanced binding to HI-Tg. The present studies show that HI-Tg is more immunogenic than LI-Tg and supports the hypothesis that a high iodine diet induces Tg autoantibodies by increasing the immunogenicity of the Tg molecule. In marked contrast with iodide-induced Tg antibodies, the Tg antibodies accompanying the severe and early-onset thyroiditis of obese strain chickens are to a large degree independent of dietary iodine intake.