Studies on the antigen reacting with the thyroid-stimulating immunoglobulin (LATS) in thyrotoxicosis.

LATS could be demonstrated in IgG but not IgA or IgM fractions of thyrotoxic sera. Changes in biological activity on fragmentation with papain or on reduction and acidification paralleled the decrease in antigen binding capacity obtained with human thyroglobulin autoantibodies treated similarly. LATS activity could be completely absorbed by homogenates of human thyroid tissue; post-mortem thyroids, non-toxic goitres, thyrotoxic glands and autonomous hyperfunctioning adenomas were all effective. Up to 23 per cent of the absorbed LATS could be recovered by acid elution under conditions known to dissociate immune complexes, whereas only 1 per cent or less of the added radioactive normal IgG marker was found in these eluates. No LATS could be extracted directly from fresh thyrotoxic glands by acid treatment. Kidney homogenates apparently inactivated about 30 per cent of the thyroid-stimulating activity of thyrotoxic sera, probably by affecting the responsiveness of the assay animal rather than by an antigen—antibody reaction involving LATS. Thus the interaction of thyroid with LATS is organ specific. Of thyroid particulate subcellular fractions, the `microsomes' were the most effective in absorbing LATS but the presumed antigen was also found in the nuclear and mitochondrial fractions. Cell sap and extracts from washed particulates were also inhibitory even after prolonged centrifugation. Some purification of the inhibitor was achieved by chromatography on DEAE-cellulose. The results obtained are consistent with the hypothesis that LATS is an auto-antibody reacting with the thyroid; the possibility that the antigen is a constituent of the plasma membrane of the epithelial cells is discussed.