Seronegative Hashimoto thyroiditis with thyroid autoantibody production localized to the thyroid.

A patient without serologic evidence of an autoimmune disorder had a thyroidectomy for neck compression caused by her goiter. Histologic examination of the gland revealed pathologic changes compatible with Hashimoto disease, and lymphocytes isolated from her thyroid gland were transformed into lymphoblastoid cells in vitro by Epstein-Barr virus in the presence of cyclosporine. These cells produced antibodies against thyroglobulin, thyroid microsome, thyrocyte membrane, and thyrotropin, whereas lymphoblastoid cells produced from the patient's peripheral blood lymphocytes showed no antithyroid activity. Several human monoclonal antibodies were produced from the intrathyroidal lymphocytes by fusion with the SHM-D33 heteromyeloma, and the resulting cell lines produced antibodies with high-affinity binding specific for thyroid antigens. These studies show that lymphocytes capable of producing antithyroid antibodies can be present in the thyroid glands of patients with Hashimoto disease without evidence of a peripheral immune response, thus indicating that Hashimoto disease can exist as an organ-restricted autoimmune disorder.

[1]  S. Nagataki,et al.  Class II major histocompatibility complex antigen expression and cellular interactions in thyroid glands of Graves' disease. , 1986, The Journal of clinical endocrinology and metabolism.

[2]  S. McLachlan,et al.  TSH RECEPTOR ANTIBODY SYNTHESIS BY THYROID LYMPHOCYTES , 1986, Clinical endocrinology.

[3]  K. Burman,et al.  Antithyrotropin antibodies in the sera of Graves' disease patients. , 1985, The Journal of clinical endocrinology and metabolism.

[4]  P. Benveniste,et al.  Studies on the immunoregulation of thyroid autoantibody production in vitro. , 1985, Clinical and experimental immunology.

[5]  L. Degroot,et al.  Identification of a thyroid microsomal antigen by Western blot and immunoprecipitation. , 1985, The Journal of clinical endocrinology and metabolism.

[6]  K. Burman,et al.  Immune mechanisms in Graves' disease. , 1985, Endocrine reviews.

[7]  S. McLachlan,et al.  Functional analysis of T and B cells from blood and thyroid tissue in Hashimoto's disease. , 1985, Clinical and experimental immunology.

[8]  A. McGregor,et al.  EVIDENCE FOR AN EFFECT OF ANTITHYROID DRUGS ON THE NATURAL HISTORY OF GRAVES' DISEASE , 1984, Clinical endocrinology.

[9]  A. McGregor,et al.  Autoimmune thyroid disease: developments in our understanding. , 1984, Endocrine reviews.

[10]  S. Filetti,et al.  Clinical experience with a human thyroid cell bioassay for thyroid-stimulating immunoglobulin. , 1984, The Journal of clinical endocrinology and metabolism.

[11]  K. Lam,et al.  Construction and testing of mouse--human heteromyelomas for human monoclonal antibody production. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[12]  D. Doniach,et al.  ABERRANT EXPRESSION OF HLA-DR ANTIGEN ON THYROCYTES IN GRAVES' DISEASE: RELEVANCE FOR AUTOIMMUNITY , 1983, The Lancet.

[13]  R. Smallridge,et al.  Partial characterization and clinical correlation of circulating human immunoglobulins directed against thyrotrophin binding sites in guinea pig fat cell membranes. Development of a direct enzyme immunoassay. , 1983, The Journal of clinical investigation.

[14]  H. Towbin,et al.  Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[15]  D. Doniach Humoral and genetic aspects of thyroid autoimmunity , 1975 .

[16]  D. Fisher,et al.  The diagnosis of Hashimoto's thyroiditis. , 1975, The Journal of clinical endocrinology and metabolism.

[17]  T. Bird,et al.  Evaluation of a tanned red cell technique for thyroid microsomal antibodies , 1973, Journal of clinical pathology.

[18]  G. Wick,et al.  Electron microscopic studies in chickens of the obese strain with spontaneous hereditary autoimmune thyroiditis. , 1972, Laboratory investigation; a journal of technical methods and pathology.

[19]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[20]  D. Doniach,et al.  Auto-antibodies in Hashimoto's disease (lymphadenoid goitre). , 1956, Lancet.

[21]  N. Rose,et al.  Studies on organ specificity. IV. Production of rabbit thyroid antibodies in the rabbit. , 1956, Journal of immunology.

[22]  T. Tötterman,et al.  Induction of circulating activated suppressor-like T cells by methimazole therapy for Graves' disease. , 1987, The New England journal of medicine.

[23]  J. Roder,et al.  In vitro stimulated lymphocytes as a source of human hybridomas , 1984, European journal of immunology.

[24]  A. Weetman,et al.  A short-term-culture ELISA system to detect IgG and autoantibody synthesis by human lymphocytes. , 1982, Journal of immunological methods.