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Detection and characterization of autoantibodies blocking the TSH-dependent cAMP production using FRTL-5 cells

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Abstract

Autoantibodies blocking the TSH-stimulated cAMP production (TBkAb) were measured in immunoglobulin G (IgG) preparations from 38 patients with primary autoimmune hypothyroidism, using FRTL-5 cells. TBkAb were detectable in 15/23 IgG preparations from patients with untreated idiopathic myxedema, and in 2/15 IgGs from patients under L-thyroxine treatment. None of the IgG from 22 normal subjects or from 10 patients with nonautoimmune hypothyroidism following total thyroidectomy caused any significant effect on the TSH-stimulated cAMP production. No correlation was found between TBkAb and the thyroid microsomal antibody. Antibodies inhibiting the 125I-TSH binding to TSH receptor were detectable in only 3/20 patients; IgGs from these 3 patients were also positive in the TBkAb assay. One IgG with potent TBkAb activity inhibited the TSH-stimulated adenylate cyclase in a competitive manner, while it had no effect on the forskolin-stimulated cAMP production. The inhibiting action of this IgG was almost completely lost after preabsorption with human thyroid membranes. In conclusion, we describe a new practical and sensitive method for the measurement of TBkAb; TBkAb are distinct from the microsomal antibody, and are probably directed to the TSH receptor.

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This work was supported by grants from the Consiglio Nazionale delle Ricerche, Progetto Finalizzato Medicina Preventiva e Riabilitativa, Sottoprogetto II (Meccanismi di Invecchiamento; grant 84.02464.56), and the Ministero della Pubblica Istruzione, Rome, Italy.

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Chiovato, L., Vitti, P., Lombardi, A. et al. Detection and characterization of autoantibodies blocking the TSH-dependent cAMP production using FRTL-5 cells. J Endocrinol Invest 10, 383–388 (1987). https://doi.org/10.1007/BF03348154

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