Human embryonic zeta-globin chains in adult patients with alpha-thalassemias.

Abstract

Human embryonic {-globin chains are a-globin-like chains that are normally present during the first three months of gestation. In this investigation, C-globin chains measured by a specific and sensitive radioimmunoassay and by an electrophoretic technique were found to be present in all 7 patients studied with hereditary Hb H disease, and in 8 out of 24 patients with a-thalassemia trait. C-Globin chains were not detected in 20 other patients with (3-thalassemia trait. These results suggest that the deletion of two a-globin genes on the same chromosome is accompanied by the continued expression of embryonic {-globin genes in adult individuals.a-Thalassemia is a hereditary disorder in which a-globin chain synthesis is either decreased or absent. It is usually caused by complete deletion of one or more a-globin genes, although partial deletion as well as nondeletion abnormalities have been described (1). In homozygous a-thalassemia with complete deletion of all four a-globin genes, the 4-globin chains, normally present during the first 3 months of gestation, continue to be synthesized even in the third trimester (2-4). These t-globin chains combine with y-globin chains to form Hb Portland-i (Q2Y2), which accounts for about 10-15% of the hemoglobins present in infants with the Hb Bart's hydrops fetalis syndrome (5, 6). These infants are usually stillborn or die shortly after birth.Hereditary Hb H disease is caused by deletion of either three a-globin genes or, rarely, two a-globin genes in combination with an abnormal a-globin gene such as a Constant Spring (1). a-Thalassemia trait is commonly the result of either the deletion of two a-globin genes from one chromosome or the deletion of one a-globin gene from each of the two homologous chromosomes (1). In this study, evidence is presented that the embryonic ;-globin genes continue to be expressed in 7 patients with hereditary Hb H disease and in 8 out of 24 other patients with a-thalassemia trait. MATERIALS AND METHODSHematological Data. Hematological parameters were determined by standard laboratory procedures, using a Coulter S electronic counter. Hemoglobin studies, including starch gel electrophoresis, determinations of Hb A2 by microcolumn chromatography (normal range 1.8-3.3%) and Hb F by the Betke method (normal range 0.4-1.2%), were done as previously described (7). Hb H inclusion bodies in peripheral blood erythrocytes were carefully searched for under a light microscope, after the blood was incubated with brilliant cresyl blue (British Drug House) for 2 hr at 37°C (8).DEAE-cellulose column chromatography (9) was performed with a number of patients' hemolysate samples and the a/f,-globin synthetic ratio in peripheral blood reticulocytes was assessed in some patients (10). Hemolysates were electrophoresed in Triton X-100/urea/polyacrylamide gels (11), and the globin bands were stained with Coomassie blue and scanned by a Beckman densitometer (model CDS-200).Isolation of Hemoglobins and Globins. Hb Portland-i (t2Y2) was partially purified from the hem...

Improved Specificity of NRBC Detection in Chorionic Villus Sample Supernatant Fluids Using Anti-Zeta and Anti-Epsilon Monoclonal Antibodies

“…The mean number of ˙-positive and Â-positive NRBCs detected in the CVS supernatant fluids from women carriers of ß-thalassemia did not differ from the rest of the samples. This is in agreement with Chung's observation that ˙-chains are not detected in hemolysates of patients with ß-thalassemia trait [13]. Based upon these observations, further studies may include determination of the number of Â-positive and ˙-positive cells as a function of carrier status of the different hemoglobinopathies.…”

“…In the case in which the mother was a carrier of ·-thalassemia, therefore she could herself produce ˙-positive chains [13], we identified the largest number of ˙-positive NRBCs. As the fetus, however, was female it was not possible to distinguish between fetal and maternal ˙-positive NRBCs.…”

Simultaneous fetal cell identification and diagnosis by epsilon-globin chain immunophenotyping and chromosomal fluorescence in situ hybridization

“…6,7 In contrast, ⑀-or -globin chains appear specific for fetal cells in chorionic villus supernatants 7 but have not been tested in maternal blood. Whereas -globin is occasionally produced in adults with ␣ thalassemia, 8 ⑀-globin has not been found in adult peripheral blood, 9 making it the preferred fetal cell identifier.…”

Detection and relocation of cord blood nucleated red blood cells by laser scanning cytometry

“…During embryonic and early fetal development, Hb Gower (Gower I: ζ 2 ϵ 2 , Gower II: α 2 ϵ 2 ) and Hb Portland (ζ 2 γ 2 ) are prevalent and detection of the zeta and epsilon chains has been used for discrimination (11, 32, 34). Whereas Hb‐ζ has been described in adults with α‐thalassemia (35), Hb‐ϵ has not been found in adult blood. Its use is restricted to a gestational age prior to the 13th week (32, 36).…”