Immunochemical studies on the thyroglobulin autoantibody system in human thyroiditis.

The binding of fluorescein-labelled thyroglobulin antibody from a Hashimoto patient to autologous thyroid could be completely inhibited by normal thyroglobulin showing that the autoantibody cannot detect any abnormality in the colloid protein from the diseased gland. Although a proportion of rabbit antisera to human thyroglobulin reacted with thyroxine, there was no evidence for such binding with human antibodies in the present studies. The heteroantibodies reacted almost identically with human and rhesus monkey thyroglobulin but much weaker cross-reactions were obtained with Hashimoto antibodies. This was related to the far smaller number of autoreactive determinants on the thyroglobulin molecule. Hashimoto sera giving a clear-line' with thyroglobulin in agar appear to react with fewer sites on the antigen than do precipitating sera, and from complexes of relatively small size in antibody excess. It was shown that sera giving horse-type' precipitin curves do not contain a mixture of avid non-precipitating antibodies with precipitating antibodies of lower affinity. It is postulated that thyroglobulin has two pairs of autoreactive determinants giving rise to two populations of antibodies. Clear-line sera contain almost exclusively one species or the other, horse-type' precipitating sera contain a preponderance of one or other species, and rabbit-type' sera contain comparable amounts of both types. A number of precipitation phenomena previously observed with Hashimoto sera can be explained on this hypothesis.