Isoelectric Focusing of Thyroid-Stimulating Antibody of Graves' Disease*

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Abstract
The thyroid-stimulating antibody (TSAb) circulating in Graves' disease can be measured by assessing its effect in vitro on the concentration of cAMP in human thyroid slices. Long-acting thyroid stimulator (LATS), also found in the blood of some patients with Graves' disease, is measured in a mouse bioassay. To test the possibility that these biological activities might reside in the same molecules and that stimulation of the mouse thyroid is due to an immunological cross-reaction, we subjected IgG from serum of patients with Graves' disease to isoelectric focusing andmeasured both activities in fractions of differing pi; antibodies to thyroglobulin, thyroid microsomal antigen, and (one serum) gastric parietal cells in the fractions also were assayed. With seven sera that were LATS positive, the peak or plateau of LATS and human thyroid slice stimulating activities coincided, predominantly in the fraction of pi 8–9; with six LATS-negative sera, maximal concentration of thyroid-stimulating antibody was in the fraction of pI 8–9 or “plateaued” around that fraction. A similar distribution of thyroid-stimulatin gactivity was seen with preparations of TSAb known to be capable of stimulating the thyroid of several nonhuman species, viz., that of mouse, guinea pig, and dog. There was no such concordance of distribution of antibodies to thyroglobulin, thyroid microsomal antigen, or parietal cells. These data support the concept that stimulation by TSAb of nonhuman thyroids, including the gland of the mouse as in the LATS bioassay, reflects cross-reaction of a thyroid antigen in nonhuman species with a human TSAb that is basically homologous to a human thyroid antigen.