Graves' IgG stimulates thyroid epithelial cell proliferation in xenotransplanted human toxic diffuse goitre

Human toxic diffuse goitre tissue was xenotransplanted to athymic mice. Transplant function was analyzed as 18 h [125I]thyroid transplant uptake at day 21 and at 10 weeks after transplantation. Graves' IgG or normal IgG was given ip daily day 22-35. Epithelial cell proliferation in the thyroid transplants was analyzed by continuous [3H]thymidine administration for 12 days between day 28 and 39 in a separate series given Graves' or normal IgG daily during the same period. The 18 h transplant uptake increased 12.8 times from 3 to 10 weeks in the Graves' IgG group but only 3.6 times in the controls (P less than 0.05). The fraction of labelled cells after [3H]thymidine incorporation was 51% +/- (SEM) after parallel Graves' IgG administration but only 2 +/- 0.3% (P less than 0.002) in the controls. The increased 10 weeks iodide uptake after Graves' IgG may be explained by an increased vascularisation or capillary maturation, by an increased individual cell sensitivity to stimulation or by an increased number of cells. Our results indicate that serum from patients with toxic diffuse goitre, i.e. Graves' IgG, contains a factor which promotes thyroid epithelial cell proliferation. Whether this is identical to TSI or is another IgG fraction remains to be shown.