Rees D C, Clegg J B, Weatherall D J
MRC Molecular Haematology Unit, Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Headington, Oxford, UK.
Blood. 1998 Sep 15;92(6):2141-6.
Hemoglobin E (HbE; alpha2beta226glu-lys), globally the commonest hemoglobin variant, is synthesized at a slightly reduced rate and has a homozygous phenotype similar to heterozygous beta thalassemia. Yet, when it is inherited together with a beta thalassemia allele, the resulting condition, HbE/beta thalassemia, is sometimes characterized by a severe, transfusion-dependent thalassemia major. The severity of this interaction has not been explained. We have explored the possibility that it may reflect the instability of HbE consequent upon globin chain imbalance imposed by the beta thalassemia allele. Time-course and pulse-chase globin chain synthesis studies at 37 degrees C on peripheral blood and bone marrow suggest that hemoglobin instability is not significant in steady-state HbE/beta thalassemia; this is confirmed by density-gradient centrifugation studies that show no decrease in HbE levels relative to HbA as HbE/beta+ thalassemia red blood cells age. Globin binding to membranes was assessed and only alpha globin chains were found, in contrast to other unstable hemoglobins in which both alpha and beta chains were present. However, in experiments performed on blood from HbE/beta thalassemics in the temperature range 39 degrees C to 41 degrees C, there was evidence of instability of HbE, a finding that was also observed in homozygous HbE. These findings suggest that the phenotype of HbE/beta thalassemia is primarily the result of the interaction of two beta thalassemia alleles; however, hemoglobin instability may be important during febrile episodes, contributing to worsening anemia.
血红蛋白E（HbE；α2β226谷氨酰胺-赖氨酸）是全球最常见的血红蛋白变异体，其合成速率略有降低，纯合子表型与杂合子β地中海贫血相似。然而，当它与β地中海贫血等位基因一起遗传时，所导致的疾病，即HbE/β地中海贫血，有时表现为严重的、依赖输血的重型地中海贫血。这种相互作用的严重程度尚未得到解释。我们探讨了一种可能性，即它可能反映了由于β地中海贫血等位基因导致的珠蛋白链失衡而引起的HbE的不稳定性。在37℃下对外周血和骨髓进行的时间进程和脉冲追踪珠蛋白链合成研究表明，在稳态HbE/β地中海贫血中血红蛋白不稳定性并不显著；密度梯度离心研究证实了这一点，该研究表明随着HbE/β+地中海贫血红细胞的老化，HbE水平相对于HbA没有下降。评估了珠蛋白与膜的结合情况，结果只发现了α珠蛋白链，这与其他同时存在α和β链的不稳定血红蛋白不同。然而，在对HbE/β地中海贫血患者血液在39℃至41℃温度范围内进行的实验中，有证据表明HbE存在不稳定性，这一发现也在纯合子HbE中观察到。这些发现表明，HbE/β地中海贫血的表型主要是两个β地中海贫血等位基因相互作用的结果；然而，血红蛋白不稳定性在发热发作期间可能很重要，会导致贫血加重。
