Biomedical subjects

H Bethäuser

Publications and source records attributed to H Bethäuser.

5 recordsLinked to original sources

PubMed1992

An autoimmuno-dominant thyroglobulin epitope characterized by a monoclonal antibody.

It has become evident in recent years that autoimmune thyroglobulin (Tg) antibodies of Graves disease and Hashimoto's thyroiditis show a restricted epitope repertoire compared to Tg heteroantibodies. We have produced monoclonal antibodies (Mab) against human Tg by the hybridoma technique and the epitope specificity was determined by crossblocking experiments. Six noncrossreactive Mabs were used in a double determinant IRMA system for plasma Tg measurements. Sensitivity of the assays was between 1 and 2 ng/ml, intraassay variation less than 5%. Recovery experiments with added Tg were performed in 25 Graves sera with elevated Tg autoantibodies. Monoclonal antibody Tg13 showed an unusual strong interference with autoantibodies resulting in a very low recovery in all sera (median: less than 10%). In further studies Tg was digested by trypsin and after Western blotting, the resulting fragments were incubated with different Mab antibodies, a polyclonal antibody and 10 different Graves sera with high Tg autoantibodies. In contrast to all other mabs only Mab Tg13 showed several low molecular weight bands between 17 and 50 KD. The major bands recognized by Mab Tg13 corresponded to bands obtained by the autoimmune sera, which showed a very homogeneous band pattern. We conclude that Mab Tg13 is specific for an autoimmunodominant B cell epitope of human Tg.

Antibodies, Monoclonal↗

PubMed1992

Description of a variably expressed and labile epitope of thyroglobulin and its occurrence in different thyroid diseases using a monoclonal antibody.

A new category of epitopes of human thyroglobulin is being described defined by a monoclonal antibody (TuTg 1). The epitope shows a very variable expression in normal individuals as well as in different thyroid diseases. According to gel filtration data the epitope is located at the intact molecule and is very sensitive to tryptic digestion. The monoclonal antibody was used in an IRMA system for plasma measurements in the follow-up of thyroid cancer patients. In individuals with high epitope expression the sensitivity to detect recurrency during T4 treatment was higher than a sensitive commercial TG IRMA.

Antibodies, Monoclonal↗

PubMed1989

Evidence for immunological differences between circulating and thyroid tissue-derived thyroglobulin in men.

The expression of six antigenic epitopes on plasma Tg and tissue-derived Tg was investigated using mouse mabs in immunoradiometric assays. The sensitivity of the assays ranged between 0.5 and 1.5 micrograms l-1. Plasma thyroglobulin of 15 normal individuals and 18 patients with metastatic, differentiated thyroid cancer was analysed. Whereas five monoclonals produced values comparable to the conventional RIA system, the monoclonal antibody Tg 158 did not detect any Tg in the normal individuals and only low levels in two of the cancer patients with the highest Tg levels. In contrast, dilutions of extracts of three different euthyroid goitre samples and three different samples of differentiated thyroid cancer revealed no difference in the antigenic expression of all six epitopes, including the Tg 158 epitope. Papain digestion of purified Tg resulted in a 76 kD fragment which showed immunoreactivity for Tg 158 as well as for Tg 11. No interference of the binding of Tg 158 by T3, T4 or DIT could be detected. We conclude that the monoclonal antibody Tg 158 detects an epitope which is present in thyroid tissue-derived Tg but not in circulating thyroglobulin. This antibody might be useful for the investigation of the secretory process of thyroglobulin from the thyrocytes into the circulation.

Antibodies, Monoclonal↗

PubMed1988

Development of immunoradiometric assays for human thyroglobulin using monoclonal antibodies and the biotin/avidin system.

Monoclonal antibodies against human thyroglobulin were produced by the hybridoma technique. Using three non-crossreactive monoclonal antibodies, an IRMA system was developed, with a polyclonal rabbit antibody fixed on microtiter plates as first extracting antibody. The monoclonal antibodies were used as second antibody, while anti-mouse IgG-biotin from goat and [125I]streptavidin served as the indicator system. The source of the monoclonal antibodies was diluted culture medium without purification. Sensitivities of 3-4 micrograms/l were obtained with all 3 monoclonal antibodies; interassay variation was about 5%. This test system will be used for further immunological characterization of circulating thyroglobulin in different thyroid diseases.

Antibodies, Monoclonal↗

PubMed1988

Comparative plasma thyroglobulin measurements with three non-cross-reactive monoclonal antibodies in metastatic thyroid cancer patients.

In 12 normal individuals and 25 patients with metastases of differentiated thyroid cancer, plasma thyroglobulin (Tg) concentrations were measured simultaneously with three immunoradiometric assays. Each of the three systems used a different, non-cross-reactive monoclonal Tg antibody as second antibody. In general, there was a very close correlation between the results of the three different systems in the cross-sectional study of the 25 cancer patients as well as in longitudinal follow-up studies in selected patients. The monoclonal antibody Tg 40 produced values about 30% higher than the two other systems. The difference was, however, not statistically significant owing to the large scatter. The monoclonal antibody Tg 13 appeared to be very sensitive to interference with thyroglobulin autoantibodies. In conclusion, the monoclonal antibodies against the three epitopes tested produced very similar Tg values in normal individuals and 25 patients with metastatic thyroid cancer; however, before more is known about epitope specificity of Tg autoantibodies and heterogeneity of tumour Tg, monoclonal antibodies should be used for routine measurements only with caution.

Antibodies, Monoclonal↗