Balb/C mice immunized with either xenogeneic or syngeneic TSH produce immunoglobulins with anti-TSH and thyroid-stimulating activities

Ben-David, Chava; Gafny, Mira; Sirkis, Nava; Gordon, Amirav; Gross, J.

doi:10.1530/acta.0.1250532

Cited by 4 publications

(2 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4). This dichotomy in the TSH receptor activation also appears in the mice immunized with xenogeneic or syngeneic TSH, as documented in our previous paper (8). A similar dichotomy could be demonstrated in the stimulating activities found in sera of Graves' patients (14)(15).…”

Section: Discussionsupporting

confidence: 84%

“…The medium was replenished with either a mixture of six hormones (6H) for cell growth or the same mixture, devoid of TSH ( 5H), for maintaining the cells in the unstimulated condition. The bioassays were a slight modification of those previously described (8). The cells were seeded in 96 well tissue culture plates and grown to confluence in 6H.…”

Section: The Bioassay Of Thyroid-stimulating Immunoglobulinsmentioning

confidence: 99%

See 1 more Smart Citation

The appearance in thyroidectomized mice of immunoglobulins that bind TSH and stimulate FRTL-5 thyrocytes

Gafny

Ben-David

Sirkis

et al. 1992

Acta Endocrinologica

Self Cite

View full text Add to dashboard Cite

The purpose of these studies was to examine whether thyroid stimulating antibodies in Graves' patients could arise as auto-antiidiotypic antibodies to endogenous anti-TSH antibodies. The model system chosen was the thyroidectomized mouse, exhibiting an elevated level of endogenous, circulating TSH. Mice were thyroidectomized by 131I administration. Sera samples were drawn 1 to 14 months later. The following activities were measured in the immunoglobulin (Ig) fractions prepared: (a) TSH binding by elisa techniques, (b) iodide pump activity (as measured by 99mTcO4 uptake) and (c) increased [3H]thymidine incorporation into the DNA of FRTL-5 cells. TSH binding Igs were detected in 29/98 mice thyroidectomized for 7\p=n-\14 months. Stimulation of technetium uptake was observed in 59/110 mice and stimulated labeled thymidine uptake in 37/102 mice, beginning eight and nine months after thyroidectomy, respectively. Of the positive animals, 51 showed a single stimulating activity. The incidence and the serum titers of Igs that stimulate technetium uptake increased significantly with time.Indeed, in the group tested 14 months post-thyroidectomy, 75% of the sera were positive for this antibody with a mean titer eightfold higher than the controls. Hybridomas were prepared from the spleen lymphocytes of thyroidectomized mice. Of these, 18 produced 99mTcO4 uptake stimulating Igs,12 [3H]thymidine-uptake stimulating Igs and 18 TSH binding Igs. Most of the hybridomas secreted Igs with a single bioactivity. One monoclonal antibody was isolated which neutralized the bioactivity of bTSH on FRTL-5 cells. 99mTcO4 uptake was decreased by 50% and [3H]thymidine uptake was virtually abolished. These results suggest that the hypothyroid mouse can develop anti-TSH antibodies and thyroid-stimulating antiidiotypic antibodies by an autoimmune process. Several pathological syndromes of the thyroid gland in the human are associated with the appearance of TSH receptor-recognizing immunoglobulins. These could be elicited as primary idiotypes against determinants on the TSH receptor ( 1 ) or as antiidiotypes to previously formed anti-TSH antibodies (abs), in accordance with the immune regulation theory of Jeme (2). The presence of both anti-bovine and anti-human bTSH abs was shown in the sera of some of the thyrotoxic patients, as reviewed by Noh et al. ( 3 ). However, the sequence of appearance of the antibodies could not be shown, neither could their idiotype-antiidiotype relationship be confirmed (4). Several experimental models were set up to examine the possibility that circulating TSH might be recognized by the immune system as nonself, and trigger thyrotoxicosis.Farid and Lo (5) immunized rats with bovine or human TSH and isolated and purified the anti-TSH antibodies which they then injected into rabbits. Some of the antiidiotypic antibodies obtained activated the TSH receptor. Costagliola et al. (6) isolated antiidiotypic abs to a mono¬ clonal anti-hTSH ab, which reacted in various ways with human TSH receptor preparations. Beall et al. (7) ...

show abstract

Section: Discussionsupporting

confidence: 84%

Section: The Bioassay Of Thyroid-stimulating Immunoglobulinsmentioning

confidence: 99%

The appearance in thyroidectomized mice of immunoglobulins that bind TSH and stimulate FRTL-5 thyrocytes

Gafny

Ben-David

Sirkis

et al. 1992

Acta Endocrinologica

Self Cite

View full text Add to dashboard Cite

show abstract

The effect of treatment with levothyroxine or iodine on thyroid size and thyroid growth stimulating immunoglobulins in endemic goitre patients

Wilders‐Truschnig

Warnkroß

Leb

et al. 1993

Clinical Endocrinology

View full text Add to dashboard Cite

Levothyroxine as well as iodine was effective in reducing thyroid size as well as thyroid growth stimulating immunoglobulins levels in endemic goitre patients. Since in both groups TSH levels were not related to thyroid size reduction, other factors than TSH suppression must be responsible for the observed thyroid size reduction. Iodine itself by virtue of its antiproliferative action on thyrocytes may have had a direct action on the goitre reduction during iodine treatment; however, the levothyroxine dose, containing less iodine, had a similar effect. A complicated picture hence emerges with regard to factors involved in the shrinkage of iodine deficiency goitre during thyroxine or iodine therapy. These findings indicate that TSH and thyroid growth promoting immunoglobulins are not the only influences on the size of endemic goitres, although it cannot be excluded that these two factors contribute to influence the pathogenetic process.

show abstract

Characterization of Monoclonal Thyroid-Stimulating and Thyrotropin Binding-Inhibiting Autoantibodies from a Hashimoto’s Patient Whose Children Had Intrauterine and Neonatal Thyroid Disease

Kohn

Suzuki

Hoffman

et al. 1997

The Journal of Clinical Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

A multiplicity of TSH receptor autoantibodies (TSHRAbs) have been characterized after subcloning heterohybridomas produced from the lymphocytes of a patient who has Hashimoto's thyroiditis and had three children with intrauterine or neonatal hyperthyroidism. Twelve clones produced stimulating TSHRAbs that increased cAMP levels and iodide uptake in rat FRTL-5 thyroid cells and increased cAMP levels in Chinese hamster ovary (CHO) cells transfected with the human TSHR; like 95% of Graves' stimulating TSHRAbs, all 12 have their functional epitope on the N-terminus of the TSHR extracellular domain, requiring residues 90-165 for activity. All 12 bind to human thyroid membranes in the absence, but not the presence, of TSH, but are only weak inhibitors of TSH binding in assays measuring TSH binding-inhibiting Igs (TBIIs). In contrast, 8 different clones produced TSHRAbs that did not increase cAMP levels, but, instead, exhibited significant TBII activity. Four inhibited the ability of TSH or a stimulating TSHRAb to increase cAMP levels and had their functional epitope on the C-terminal portion of the TSHR external domain, residues 261-370, mimicking the properties of blocking TSHRAbs that cause hypothyroidism in patients with idiopathic myxedema. The 4 other TBIIs inhibited the ability of TSH, but not that of a stimulating TSHRAb, to increase cAMP levels, like TBIIs in Graves' patients. The functional epitope for 3 of these Graves'-like TBIIs was residues 90-165; the functional epitope for the fourth was residues 24-89. The fourth also increased arachidonic acid release and inositol phosphate levels in FRTL-5 thyroid cells and exhibited conversion activity, i.e. the ability to increase cAMP levels in the presence of an anti-human IgG. Thus, this TBII exhibited signal transduction activity, unlike the other 3 Graves'-like TBIIs. The patient, therefore, has stimulating TSHRAbs and 3 different types of TBIIs, each with different functional properties and different epitopes on the TSHR.

show abstract

Balb/C mice immunized with either xenogeneic or syngeneic TSH produce immunoglobulins with anti-TSH and thyroid-stimulating activities

Cited by 4 publications

References 15 publications

The appearance in thyroidectomized mice of immunoglobulins that bind TSH and stimulate FRTL-5 thyrocytes

The appearance in thyroidectomized mice of immunoglobulins that bind TSH and stimulate FRTL-5 thyrocytes

The effect of treatment with levothyroxine or iodine on thyroid size and thyroid growth stimulating immunoglobulins in endemic goitre patients

Characterization of Monoclonal Thyroid-Stimulating and Thyrotropin Binding-Inhibiting Autoantibodies from a Hashimoto’s Patient Whose Children Had Intrauterine and Neonatal Thyroid Disease

Contact Info

Product

Resources

About