Study of circulating immune complexes in thyroid disease. Comparison of Raji cell RIA and specific thyroglobulin-anti-thyroglobulin radioassay

Circulating soluble immune complexes (ICs) were studied by Raji cell RIA in a series of patients with and without thyroid disorders. Clearly elevated IC levels (>41.2 εgeq/ml; i.e. >3 SD above the mean value of the normal controls) were found in 3 of 18 patients with Hashimoto's thyroiditis, in 4 of 39 with differentiated thyroid carcinoma, and in none of 21 patients with Graves' disease as well as in none of 21 normal healthy controls. Thyroglobulin (Tg) was not found in the ICs bound to Raji cells when sought by a sensitive radiolabeled antibody technique. Furthermore, experiments carried out with radiolabeled Tg-anti- Tg ICs (Tg-ICs) obtained by mixing Tg with homologous (Hashimoto's sera) antibody revealed that homologous Tg-ICs did not bind to Raji cells, while the ICs prepared from heterologous (rabbit) antibody did bind. Tg-ICs were also assayed in the same sera and in additional samples from 29 normal controls and 12 patients with Graves' disease by a recently developed specific immunoradiometric assay (Takeda, Y., and J. P. Kriss, J Clin Endocrinol Metab 44: 46, 1977). Lower levels of Tg-ICs (22–262 ng⁄ml) than those detectable by Raji cell RIA were shown in 5.5‰ of the patients with Hashimoto's thyroiditis, 38.2‰ of those with Graves' disease, and 33.2‰ of those with differentiated thyroid carcinoma. No correlation was found between these results and the IC levels assessed by Raji cell RIA. Our data suggest that both Tg-ICs and complexes unrelated to Tg are present in sera of patients with thyroid autoimmune disorders and thyroid carcinoma. The ICs detected by the Raji cell method must not contain Tg, since 1) they occur in patients who are negative by the specific Tg-IC assay, 2) they are present in concentrations nearly 1000-fold higher than Tg-ICs, 3) Tg cannot be detected in the ICs bound to the Raji cells, and 4) Tg- ICs prepared from human antibody did not bind to Raji cells. The possible pathogenic role of these substances remains to be established. The failure of Tg-ICs to fix complement (and thus bind to Raji cells) may explain why IC disease is not a characteristic feature of autoimmune thyroid diseas