Monoclonal autoantibody to thyroglobulin as a possible vector in immunodiagnosis and immunotherapy of differentiated thyroid cancer.

Abstract

Differentiated thyroid carcinoma synthetize and secrete thyroglobulin. During its biosynthesis this antigen becomes expressed in the microvilli-bearing surface of carcinoma cells. Attempts have been carried out to target, with specific antithyroglobulin antibodies, the membrane bound absorption thyroglobulin in cancer cells for in vivo diagnosis and therapy. In the serum of patients with autoimmune thyroid diseases a high concentration of antithyroglobulin antibodies is frequently found (1-3 mg/ml). Their purification by immunoabsorption and dissociation is hampered by a low recovery and partial denaturation. It has been recently reported that about 1% of sera from Hashimoto's thyroiditis bear in their electrophoretogram a "myeloma-like protein". In the present report we describe in the serum of a Hashimoto patient a myeloma-like IgG which is an antithyroglobulin autoantibody with restricted functional and structural properties. The serum concentration of this myeloma-like IgG was found to be 40 mg/ml with a capacity of 6.5 nM of human thyroglobulin/mg IgG. The light chain composition was determined to be mostly of the lambda type. The clonal analysis of this myeloma IgG carried out by isoelectrofocusing, immunoblotting and autoradiography resulted in the recognition of several distinct clones, two of which were prominent at pH 8.7 and 7.8. By this technique and in view of the high serum concentration of this myeloma-like IgG, single clones of antithyroglobulin autoantibody can be easily obtained in high yields and without denaturation from human serum. This reagent could offer an ideal immunovector to target membrane-bound thyroglobulin of cancer cells.