Binding of Reverse Triiodothyronine to Serum Immunoglobulins in Man and the Rabbit*

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Abstract
In a boy with lymphocytic thyroiditis, paper electrophoresis of serum showed not only specific antibodies for T4 and T3 but also demonstrated pronounced antibody activity to rT3, as noted by the binding of exogenously added [125I]rT3 by γ-globulins. The antibody binding of [125I]rT3 could be inhibited by prior equilibration of the patient’s serum with an excess of nonradioactive T4 but not with T3. To further define the nature of rT3 antibody activity, T4, T3, and rT3 specific antibodies were also produced experimentally in rabbits by active immunization with iodothyronine-albumin conjugates. Antibody binding of rT3 similar to that noted in the patient’s serum was also observed in rabbit T4 antiserum; furthermore, rT3 antibody-binding activity could be inhibited by prior equilibration with nonradioactive T4 but not T3. The similarity of the rT3-antibody interaction in unsaturated serum and in T3- or T4-loaded serum from the patient and a T4-immunized rabbit as well as other paper electrophoretic studies with tracer iodothyronines and their specific antisera suggested that the antigen-combining sites of T3 and rT3 antibodies are distinct. In the case of T4 antibody, the antigenic specificity is shared with rT3 because of the structural similarity to T4. In contrast to rT3−, T4−, and T3−immune binding in the patient‚s serum, rT3-specific rabbit antiserum did not exhibit significant T3 or T4 cross-reactivity. It is concluded that circulating rT3-binding antibodies in our patient are indeed T4 antibodies interacting with rT3.