Hervé F, Duché J C, Jaurand M C
INSERM U 139, UFR Médecine Paris XII, Créteil, France.
J Chromatogr B Biomed Sci Appl. 1998 Sep 11;715(1):111-23. doi: 10.1016/s0378-4347(98)00085-1.
Human alpha1-acid glycoprotein (AAG), an acute-phase plasma protein, is heterogeneous in the native state and polymorphic in the desialylated state. The AAG heterogeneity is mainly explained by a variable glycan chain composition in its five glycosylation sites. The AAG polymorphism is due to the presence of genetic variants. Three main variants are observed for AAG, ORM1 F1, ORM1 S and ORM2 A, which have a separate genetic origin. In this paper, we have used different isoelectric focusing (IEF) methods and chromatography on immobilized metal affinity adsorbent to study the relative occurrence of the genetic variants of AAG in relation to changes in microheterogeneity, in plasma and pleural effusions of patients with malignant mesothelioma (MM). The results were compared to those obtained with the variants in plasma of healthy individuals. Significant changes in variant distribution were observed in the MM samples, that corresponded to a rise in the proportion of the ORM1 variants and a fall in that of the ORM2 variant. However, the concentration in MM plasma increased for both variants. The AAG in MM plasma and effusion fluids was found to be more heterogeneous on IEF than AAG of healthy plasma. The evidence of stronger concentrations of both the high and low pI forms of AAG in the MM samples suggested two kinds of changes in charge heterogeneity. These two changes were shown to be attributed to different variants--i.e. the high pI forms to ORM1 F1 and S and the low pI forms to ORM2 A, after fractionation of AAG by chromatography on immobilized copper(II) ions. These results indicate specific changes in both the expression and glycosylation for each AAG variant, according to its separate genetic origin, in MM.
人α1-酸性糖蛋白（AAG）是一种急性期血浆蛋白，在天然状态下具有异质性，在去唾液酸化状态下具有多态性。AAG的异质性主要由其五个糖基化位点中可变的聚糖链组成来解释。AAG的多态性是由于遗传变异的存在。观察到AAG有三种主要变体，即ORM1 F1、ORM1 S和ORM2 A，它们有独立的遗传起源。在本文中，我们使用了不同的等电聚焦（IEF）方法和固定化金属亲和吸附剂色谱法，来研究恶性间皮瘤（MM）患者血浆和胸腔积液中AAG遗传变体的相对发生率与微异质性变化的关系。将结果与健康个体血浆中变体的结果进行比较。在MM样本中观察到变体分布有显著变化，这对应于ORM1变体比例的上升和ORM2变体比例的下降。然而，两种变体在MM血浆中的浓度都增加了。发现MM血浆和积液中的AAG在IEF上比健康血浆中的AAG更具异质性。MM样本中AAG高和低pI形式浓度更高的证据表明电荷异质性有两种变化。通过固定化铜（II）离子色谱法对AAG进行分级分离后，这两种变化被证明归因于不同的变体，即高pI形式归因于ORM1 F1和S，低pI形式归因于ORM2 A。这些结果表明，在MM中，根据其独立的遗传起源，每种AAG变体在表达和糖基化方面都有特定变化。
