Thyroid-Stimulating Activity in the Serum of Rabbits Immunized with Thyroid Microsomes

Abstract

Rabbits were immunized with human thyroid microsomes in an effort to determine if thyroid-stimulating activity would develop in their serum. Twenty-four of 32 rabbits so immunized developed significant amounts of thyroid-stimulating activity, while only 1 of 8 control animals, immunized with liver or adrenal microsomes, had such a response. Peak thyroidstimulating activity appeared in most instances one week after the course of immunization; it usually declined thereafter. Repeated courses of immunization resulted in the appearance in serum of larger amounts of thyroid-stimulating activity. Active rabbit serums generally caused a murine blood 131 I response which was slightly higher at 2 than at 8 hr and was intermediate in time course between thyrotropin and the longacting thyroid stimulator. The serum of thyroidimmunized rabbits showed an elevated PBI and thyroxine, balanced by markedly reduced resin uptake of 131 I-triiodothyronine (T 3 ). Thyroidal 131 I uptake and serum PB 131 I and conversion ratio were unaffected by immunization. The serum of thyroid-immunized rabbits contained precipitating and hemagglutinating antibodies against human thyroglobulin and antibodies which fixed to both colloid and cytoplasm of thyroid tissue sections. These serums also contained complement-fixing antibodies against human thyroid microsomes, but serums from liverimmunized rabbits also caused complementfixation. The immunofluorescent reaction in thyroid cytoplasm was also nonspecific. It is concluded that serum thyroid-stimulating activity does develop, along with various antithyroid antibodies, in rabbits immunized with human thyroid microsomes; the affected rabbits appear to remain euthyroid. {JClin Endocr28: 503,1968)

Effects of Antithyroid Therapy on the Long-Acting Thyroid Stimulator and the Antithyroglobulin Antibodies1

“…(J Clin Endocr 29: 231,1969) E VIDENCE indicating that the longacting thyroid stimulator (LATS) is involved in the pathogenesis of Graves' disease has been extensively discussed (1,2). The hypothesis that LATS is an antibody to a thyroid antigen (3), has received support from the finding of thyroid-stimulating activity in the serum of rabbits immunized with human thyroid tissue (4)(5)(6)(7). A significant correlation between LATS and high titers of antithyroglobulin antibodies has been found in patients with active Graves' disease (8,9).…”

Comparative Studies on the Properties of LATS and TSH

“…There are several reports of LATS crossing the placenta (McKenzie, 1964;Sunshine et al, 1965), which are compatible with LATS being an antibody. Further, gamma globulin antibody having thyroid stimulating activity is produced by immunization of rabbits with human thyroid cell fraction (Beall and Solomon, 1968;McKenzie, 1968). In previous experiments, we were unable to detect a "LATS" antigen by the passive cutaneous anaphylaxis technique or the indirect immunofluorescent method, and to this time , no clear immunological reaction has confirmed that an antigen for LATS is present in the components of the thyroid cell (Ochi and DeGroot, 1968).…”

In vitro Tests of Thyroid Function in Active Thyroglobulin Immunity

“…The antibody binding of thyroxine (T4) in active thyroid immunity, a phenomenon originally described in this laboratory based on electrophoretic distribution of radiothyroxine in immune sera ( l ) , has now been confirmed in various other laboratories (2)(3)(4)(5)(6). Miore recent investigations in obese strain chickens have also shown binding of thyrmine by spontanmusly forming thyroid autoantibodies (7).…”

“…In passive immunity there is no exogenous antigen challenge or de novo antibody synthesis, rather antibodies from an immune subject or an animal are merely transferred to another individual either naturally (e.g., passage of antibody gamma globulin, IgG, through the placenta) or artificially through exogenous administration. 3 On leave from the Radiobiology Division, Atomic Energy Establishment, Cairo, Egypt. T4-thyroid antibody interaction, we have carried out some in vitro tests of thyroid function simultaneously with paper electrophoretic studies in the sera of thyroglobulinimmunized animals.…”