Anti-thyrotrophin receptor antibodies in Graves' disease as demonstrated directly by immunoprecipitation assay

1983 ◽  
Vol 102 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Tjerk W. A de Bruin ◽  
Daan van der Heide ◽  
Maria C. Krol

Abstract. An immunoprecipitation assay was developed to determine the presence of antibodies against human TSH1 receptors. With this assay we were able to demonstrate that in comparison with sera from normal controls, 24 out of 30 (80%) sera from patients with untreated Graves' disease could immunoprecipitate more [125I]TSH-TSH receptor complexes. In 9 assays, an average of 14.1 ± 3.7% (sd) of the [125I]TSH-TSH receptor complexes was immunoprecipitated by the 30 Graves' sera vs 9.8 ± 3.0% by the normal pool serum (n = 23) (P < 0.001) and 7.7 ± 2.8% by the 22 normal sera (P < 0.001). One serum of the 24 positive Graves' sera was studied in detail. The results suggest that this serum contained an anti-TSH receptor auto-antibody directed towards a different determinant on the TSH receptor than the TSH binding site.

1984 ◽  
Vol 105 (3) ◽  
pp. 330-340 ◽  
Author(s):  
Tjerk W. A. de Bruin ◽  
Daan van der Heide ◽  
Maria C. Krol

Abstract. The effect of the anti-TSH receptor antibodies present in the sera of 8 patients with Graves' disease on the affinity constant (Ka) and the number (R) of TSH receptors in autologous human thyroid plasma membranes was investigated. Kinetic analysis of [125I]bTSH binding to human thyroid plasma membranes in the presence of autologous Graves' and normal gammaglobulins was carried out by means of a computer fitting programme. Analysis of the TSH-TSH receptor interaction in the presence of TSH alone yielded curvilinear Scatchard plots, indicating the existence of two independent classes of binding sites (high affinity Ka: 8.5 ± 4.8 × 108 m−1; low affinity Ka: 5.3 ± 2.7 × 106 m−1). Similarly the Scatchard plot for this interaction in the presence of normal gammaglobulins is also curvilinear. Linear Scatchard plots, indicating the existence of only one class of high affinity TSH binding sites (Ka: 3.5 ± 1.8 × 108 m−1), were obtained for both autologous gammaglobulins and pure IgG from 8 patients with Graves' disease. The number of high affinity TSH binding sites in the presence of Graves' gammaglobulins had increased on the average by a factor 3.76 ± 0.74 (sd) with respect to the number found in the presence of normal gammaglobulins. This marked change in the kinetic behaviour of the TSH binding sites provided evidence that there is a direct interaction between anti-TSH receptor antibodies and autologous TSH receptors. Divalency of Graves' IgG or linkage of Fab fragments by anti-Fab antiserum proved to be necessary to produce this specific change in the kinetic behaviour of TSH binding sites. Graves' IgG monovalent Fab and Fc fragments had no effect. We suggest that the mechanism by which anti-TSH receptor antibodies in Graves' disease mimick the biological action of TSH is the IgG-induced cross-linkage of TSH receptors.


2020 ◽  
Vol 93 (6) ◽  
pp. 417-419
Author(s):  
Aina Scatti Regàs ◽  
Ricard Pujol Borrell ◽  
Roser Ferrer Costa ◽  
Elsa Puerto Carranza ◽  
María Clemente León

The Lancet ◽  
1988 ◽  
Vol 331 (8575-8576) ◽  
pp. 14-17 ◽  
Author(s):  
Nobuo Matsuura ◽  
Kenji Fujieda ◽  
Yasuhiro Iida ◽  
Seiichiro Fujimoto ◽  
Junji Konishi ◽  
...  

2011 ◽  
Vol 57 (3) ◽  
pp. 17-20
Author(s):  
M S Sheremeta ◽  
N Iu Sviridenko ◽  
I M Belovalova ◽  
P I Garbuzov

The primary objective of the present work was to study the clinical course of endocrine ophthalmopathy (EOP) following radioiodine therapy (RIT) of Graves' disease (GD) and depending on its effect (development of post-radiation hypothyroidism). The secondary objective was to determine risk factors of EOP progression after radioiodine therapy. This prospective study included 38 patients (76 eyes) allocated to two groups. The patients of group 1 (n=19/38 eyes) presented with thyrotoxicosis at each visit and continued to use thyrostatic agents; those in group 2 (n=19/38 eyes) had hypothyroidism at its early stages (3 and 6 months) and were given substitution therapy with levothyroxin. The development of post-radiation hypothyroidism was shown to strongly influence the clinical course of EOP. In the patients of group 1, EOP remained active throughout the entire observation period (12 months) in the absence of appreciable variations of its integral severity index. In group 2, the same index decreased significantly, but active forms of EOP could be detected by the time of onset of hypothyroidism (6 months) (p=0.0000). After 12 months, the level of anti-TSH receptor antibodies in the patients of group 1 was significantly higher than in those of group 2 (10.8±8.3 and 2.9±2.0 respectively, p=0.0003). The regression rate of EOP symptoms following radioiodine therapy (RIT) of Graves' disease was a function of the efficacy of thyroid 131I radioablation. It is concluded that persistence of anti-TSH receptor antibodies was responsible for the deterioration of the clinical picture of endocrine ophthalmopathy after radioiodine therapy.


2008 ◽  
Vol 158 (1) ◽  
pp. 69-75 ◽  
Author(s):  
Peter Laurberg ◽  
Göran Wallin ◽  
Leif Tallstedt ◽  
Mirna Abraham-Nordling ◽  
Göran Lundell ◽  
...  

IntroductionAutoimmunity against the TSH receptor is a key pathogenic element in Graves' disease. The autoimmune aberration may be modified by therapy of the hyperthyroidism.ObjectiveTo compare the effects of the common types of therapy for Graves' hyperthyroidism on TSH-receptor autoimmunity.MethodsPatients with newly diagnosed Graves' hyperthyroidism aged 20–55 years were randomized to medical therapy, thyroid surgery, or radioiodine therapy (radioiodine was only given to patients ≥35 years of age). l-thyroxine (l-T4) was added to therapy as appropriate to keep patients euthyroid. Anti-thyroid drugs were withdrawn after 18 months of therapy. TSH-receptor antibodies (TRAb) in serum were measured before and for 5 years after the initiation of therapy.ResultsMedical therapy (n=48) and surgery (n=47) were followed by a gradual decrease in TRAb in serum, with the disappearance of TRAb in 70–80% of the patients after 18 months. Radioiodine therapy (n=36) led to a 1-year long worsening of autoimmunity against the TSH receptor, and the number of patients entering remission of TSH-receptor autoimmunity with the disappearance of TRAb from serum during the following years was considerably lower than with the other types of therapy.ConclusionThe majority of patients with Graves' disease gradually enter remission of TSH-receptor autoimmunity during medical or after surgical therapy, with no difference between the types of therapy. Remission of TSH-receptor autoimmunity after radioiodine therapy is less common.


Sign in / Sign up

Export Citation Format

Share Document