Biomedical subjects
Publications and source records attributed to T Komaki.
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Recently anti-thyroid hormone antibodies have been found in many cases of thyroidal and non-thyroidal disorders. However, the exact mechanism(s) of production of anti-thyroid hormone antibodies in these patients is so far obscure. Thyroxine (T4) and triiodothyronine (T3) are haptens and are not immunogenic in free form. In this respect, human thyroglobulin (HTg) has long been suggested as an antigen of the anti-thyroid hormone antibodies observed in them because it carries thyroid hormones on its surface. In our previous communication, we reported the production of anti-HTg antibodies and anti-thyroid hormone antibodies in two rabbits and various strains of mice immunized with HTg. In order to elucidate the gene(s) which controls the production of anti-HTg and anti-thyroid hormone antibodies, various strains of mice which have different H-2 and Igh allotypes were immunized with HTg. The titers of anti-HTg and anti-thyroid hormone antibodies were measured, and the locus (loci) which controls the immune response against them was determined. Our present investigation has revealed that the Ir-gene(s) which controls the production of anti-HTg and anti-T4 antibodies is located in the I-A subregion. Concerning the production of anti-T4 antibodies in mice, the presence of Ir-gene(s) outside of H-2 is also suggested. The significance of the genetic mechanisms controlling the immune response against thyroid hormones in various thyroidal disorders is discussed.
A very simple method for the evaluation of the interaction between thyroxine binding globulin (TBG) and thyroxine (T4) has been developed and evaluated in 6 healthy subjects and 5 pregnant women. Rabbit anti-human TBG antiserum was precipitated with 50% ammonium sulfate followed by passing a DEAE-cellulose column. Immunoglobulin G (IgG) fraction thus prepared was covalently attached on a Sepharose CL-4B and used as an immunoadsorbent of serum TBG. After treatment with charcoal to remove endogeneous thyroid hormones, 10 microliter of sera from 6 healthy subjects and 5 pregnant women were incubated with 125I-T4 and various concentrations of cold T4 followed by immunoadsorption with anti-TBG-Sepharose, and association constants (Ka) between TBG and T4 were calculated in each subject using Scatchard's plot. The Ka value thus obtained in 6 healthy subjects was 1.47 X 10(8) M-1 (SD = 0.24), and in 5 pregnant women it was 0.82 X 10(8) M-1 (SD = 0.21) which was significantly lower than that of healthy subjects (P less than 0.001). Our present method does not need purification of TBG from serum to investigate its functions, especially in relation to the binding with thyroid hormones. Also, only a very small amount (100 approximately 150 microliter) of serum is enough for the calculation of Ka between T4 and TBG. The whole procedure is very easy to perform and can be done in a relatively short time, and therefore we consider this method clinically relevant and useful.
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