Development of Radioimmunoassay for Serum Transferrin Receptor and Its Clinical Application

The transferrin receptor is a transmembrane glycoprotein composed of two disulfide-linked 95,000 molecular weight subunits, and has an essential role to deliver iron-loaded transferrin into the cells. In the present paper, a new purification method of the transferrin receptor from human placenta and evidence of a circulating transferrin receptor in the sera using a sandwich radioimmunoassay are described. The results obtained were as follows; （1） Transferrin receptor with a molecular weight of 95,000 daltons was isolated from human placenta by a combination of Sephacryl S-300 column chromatography and affinity chromatography immobilized with anti-transferrin antibody. The yield of the receptor was about 0.8 mg from 500g of the placenta. （2） A quantitative method for measuring immunoreactive transferrin receptor by using anti-transferrin receptor monoclonal antibodies, B3/25 and OKT9 was developed. Circulating transferrin receptor was detected in human serum with this assay and the mean concentrations of the serum transferrin receptor in healthy males and females were 251±94 （mean±SD） ng/ml and 256±99ng/ml, respectively. （3） The mean serum transferrin receptor concentration of patients with iron deficiency anemia （IDA）, autoimmune hemolytic anemia（AIHA） and aplastic anemia were 730±391ng/ml, 1452±1078ng/ml and 182±39ng/ml, respectively. The values of those with IDA and AIHA were significantly higher than that of normal controls and the values for aplastic anemia were lower that that of normal controls. （4） The mean serum transferrin receptor concentration of patients with polycythemia vera and secondary polycythemia, bone morrow findings of which are usually very cellular, were 800±125ng/ml and 1033±203ng/ml, respectively. Both of them were significantly higher than that of normal controls. （5） There was a good correlation between serum transferrin receptor values and reticulocyte counts in patients with IDA, AIHA and aplastic anemia. In patients with IDA, serum transferrin receptor values had a significant positive correlation with total iron binding capacity and significant negative correlations with serum iron and serum ferritin concentration, whereas no correlations were observed in AIHA and aplastic anemia. Therefore, the number of circulating transferrin receptors in patients with anemia and polycythemia may reflect the level of bone marrow erythropoiesis and is a potential new index for red cell production.departmental bulletin pape