Abstract
Few autoantibodies directed against thyroglobulin (TgAbs) have been fully characterized in man. The present study was designed to characterize TgAbs from patients with unusually high titers (> 1: 512) using the tanned red cell hemagglutination technique (TRC). IgG was isolated from the sera of subjects with Hashimoto’s thyroiditis (n = 4), subacute thyroiditis (n = 1) and Graves’ disease (n = 1) using DEAE-Sephacel chromatography. Isolated TgAbs were substituted as first antibody in a double antibody thyroglobulin (Tg) RIA and the Ka’s were determined by Scatchard analysis. Molecular ratios of antibody to antigen, TgAb: Tg, were calculated from quantitative precipitin curves. The clonality of each antibody was determined using agarose isoelectric focusing and131 I labeled Tg as an autoradiographic probe. All six TgAbs were polyclonal. The Ka’s were on the order of 109–1010. In two sera TgAb: Tg ratios of 20: 1 and 8: 1 were obtained. These results are significant when compared to previously characterized Tg autoantibodies which have been of low titer, low Ka (105), and have been directed towards a restricted portion of the Tg molecule (TgAb: Tg ratios of 2: 1 to 6:1). In view of their high affinity constants and recognition of a less restricted portion of the Tg molecule, some of the TgAb’s with unusually high titers behave more like Tg heteroantibodies than autoantibodies.
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Roitt I.M., Doniach D., Campbell P.N., Vaughan H.E. Autoantibodies in Hashimoto’s disease. Lancet 2: 820, 1956.
Roitt I.M., Doniach D., Campbell P.N. The nature of the gamma globulins in lymphadenoid goitre. Biochem. J. 64: 54 P., 1956.
Roitt I.M., Campbell P.N., Doniach D. The nature of the thyroid autoantibodies present in patients with Hashimoto’s thyroiditis (Lymphadenoid Goitre). Biochem. J. 69: 248, 1958.
Doniach D., Roitt I.M. Auto-immunity in Hashimoto’s disease and its implications. J. Clin. Endocrinol. Metab. 17: 1293, 1957.
Witebsky E., Rose N.R. Studies on organ specificity. IV. Production of rabbit thyroid antibodies in the rabbit. J. Immunol. 76: 408, 1956.
Rose N.R., Witebsky E. Studies on organ specificity. V. Changes in the thyroid glands of rabbits following active immunization with rabbit thyroid extracts. J. Immunol. 76: 417, 1956.
Shulman S., Witebsky E. Studies on organ specificity. IX. Biophysical and immunohistochemical studies on human thyroid autoantibody. J. Immunol. 85: 559, 1960.
Stokinger H.E., Heildeberger M. A quantitative theory of precipitin reaction. VI. The reaction between mammalian thyroglobulins and antibodies to homologous and heterologous preparations. J. Exp. Med. 66: 251, 1937.
Heidelberger M. The molecular composition of specific immune precipitates from rabbit sera. J. Am. Chem. Soc. 60: 242, 1938.
Dussault J.H., Guay D. Qualitative aspects of thyroglobulin antibodies in Hashimoto’s thyroiditis and Graves’ disease. Can. Med. Ass. J. 111: 319, 1974.
Nye L., Pontes De Carvalho L.C., Roitt I.M. Restrictions in the response to autologus thyroglobulin in the human. Clin. Exp. Immunol. 41: 252, 1980.
Berson R.A., Yalow R.S. Quantitative aspects of the reaction between insulin and insulin-binding antibody. J. Clin. Invest. 38: 1996, 1959.
Ruf J., Carayon P., Lissitzky S. Various expression of a unique anti-human thyroglobulin antibody repertoire in normal state and autoimmune disease. Eur. J. Immunol. 15: 268, 1985.
Ruf J., Carayon P., Sarles-Philip N., Koorilsky F., Lissitzky S. Specificity of monoclonal antibodies againts human thyroglobulin; comparison with autoimmune antibodies. EMBO J. 2: 1821, 1983.
Lowry C.H., Rosebrough N.J., Farr A.L., Randall R.J. Protein measurement with the folin phenol reagent. J. Biol. Chem. 193: 265, 1951.
Van Herle A.J., Uller R.P., Matthews N.L., Brown J. Radioimmunoassay for measurement of thyroglobulin in human serum. J. Clin. Invest. 52: 1320, 1973.
Greenwood F.C., Hunter W.M. The preparation of 131 I-labeled human growth hormone of high specific radioactivity. Biochem. J. 89: 114, 1963.
Heidelberger M., Kendall F.E. A quantitative study of the precipitin reaction between type III pneumococcus polysaccharide and purified homologous antibody. J. Exp. Med. 50: 809, 1929.
Scatchard G. The attraction of proteins for small molecules and ions. Ann. N.Y. Acad. Sci. 51: 660, 1949.
Hudson L., Hay F.C. Praticai Immunology. Blackwell Scientific Publications, Oxford 1976, p. 107.
White R.G. Discussion on autoimmunity and thyroiditis. Proc. R. Soc. Med. 50: 953, 1957.
Nye L., Pontes De Carvalho L.P., Roitt I.M. An investigation of the clonality of human autoimmune thyroglobulin antibodies and their light chains. Clin. Exp. Immunol. 46: 161, 1981.
Michaelson T.E., Gaarder P.I., Kornstad L. A transient monoclonal IgGlk protein with antithyroglobulin activity: lack of cross-idiotypy with polyclonal antithyroglobulin antibodies. Clin. Exp. Immunol. 46: 268, 1981.
Weigle W.O., Roball C.G. Relationship among the levels of self proteins immune states of Tg and cells and autoimmunity. In: Pinchera A., Doniach D., Fenzi G.F., Baschieri L. (Eds.), Autoimmune aspects of endocrine disorders. Academic Press, New York 1980, p. 39.
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This work was presented in abstract form at the 9th International Thyroid Congress, Sao Paulo, Brasil 1985.
This work was partially supported by Cancer Research Coordinating Committee Grant No. A850702.
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Costin, A., Klandorf, H., Persselin, J. et al. Characterization of high titer antithyroglobulin antibodies. J Endocrinol Invest 10, 541–546 (1987). https://doi.org/10.1007/BF03346990
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DOI: https://doi.org/10.1007/BF03346990