Dover G J, Chang V T, Boyer S H, Serjeant G R, Antonarakis S, Higgs D R
Blood. 1987 Jan;69(1):341-4.
Fetal hemoglobin (HbF) levels vary widely among individuals with sickle cell anemia (SS). Previous studies have suggested that HbF levels in SS individuals with alpha-thalassemia (two or three functional alpha-globin genes) are lower than HbF levels in SS individuals with four normal alpha-globin genes. Using immunocytochemical techniques, we studied F cell production as measured by % F reticulocytes, the amount of HbF per F cell, and the preferential survival of F cells versus non-F cells in 51 subjects with four alpha genes, 32 subjects with three alpha genes, and 18 subjects with two alpha genes. Comparison between alpha-globin gene groups was performed for the total sample as well as for a subset of 82 individuals who had replicate samples and a further subset of 39 age-matched individuals. %HbF levels were 6.8, 4.9, and 4.5 percent for the total four-, three-, and two-alpha-globin-gene groups, respectively. The percentage of F reticulocytes, percentage HbF per F cell, and the enrichment ratio (% F cell/% F reticulocytes) did not change significantly with alpha-globin gene number. Moreover, no correlation existed between alpha-globin gene number and the absolute number of F cells in any group studied. However, there was a strong inverse correlation (r = -0.407, P = .0001) between non-F cell levels (1.7 +/- 2, 2.2 +/- 5, 3.0 +/- 1.0 X 10(12)/L) and decreasing alpha-globin gene number. These data suggest that falling HbF levels among SS individuals with lessened numbers of alpha-globin genes reflect prolonged survival of non-F cells and are not due to intrinsic differences in F cell production or in the amount of HbF per F cell. The improved survival of non-F cells in SS alpha-thalassemia is presumed to be due to the lower MCHC observed in such individuals.
胎儿血红蛋白（HbF）水平在镰状细胞贫血（SS）患者中个体差异很大。先前的研究表明，患有α地中海贫血（两个或三个功能性α珠蛋白基因）的SS患者的HbF水平低于具有四个正常α珠蛋白基因的SS患者的HbF水平。我们使用免疫细胞化学技术，研究了51名具有四个α基因、32名具有三个α基因和18名具有两个α基因的受试者中，以F网织红细胞百分比衡量的F细胞生成、每个F细胞的HbF量以及F细胞与非F细胞的优先存活率。对整个样本以及82名有重复样本的个体子集和39名年龄匹配个体的进一步子集进行了α珠蛋白基因组之间的比较。四个、三个和两个α珠蛋白基因组的总HbF水平分别为6.8%、4.9%和4.5%。F网织红细胞百分比、每个F细胞的HbF百分比以及富集率（F细胞百分比/F网织红细胞百分比）并未随α珠蛋白基因数量的变化而显著改变。此外，在所研究的任何组中，α珠蛋白基因数量与F细胞的绝对数量之间均无相关性。然而，非F细胞水平（1.7±2、2.2±5、3.0±1.0×10¹²/L）与α珠蛋白基因数量减少之间存在强烈的负相关（r = -0.407，P = 0.0001）。这些数据表明，α珠蛋白基因数量减少的SS患者中HbF水平下降反映了非F细胞的存活时间延长，而非由于F细胞生成或每个F细胞的HbF量存在内在差异。SS型α地中海贫血中非F细胞存活率的提高被认为是由于此类个体中观察到的较低平均血红蛋白浓度（MCHC）所致。
