Klintworth G K, Meyer R, Dennis R, Hewitt A T, Stock E L, Lenz M E, Hassell J R, Stark W J, Kuettner K E, Thonar E J
Ophthalmic Paediatr Genet. 1986 Dec;7(3):139-43. doi: 10.3109/13816818609004130.
An ELISA assay using a monoclonal antibody (ET-4-A-4) that recognizes a sulfated carbohydrate epitope in both keratan sulfate type I (corneal) and type II (skeletal) was employed to quantify keratan sulfate in serum and corneal tissue from patients with macular corneal dystrophy (MCD). This assay disclosed significant quantities of keratan sulfate in the serum in 45 healthy individuals (251 +/- 78 ng/ml), and in 66 patients with various corneal diseases (273 +/- 101 ng/ml). In contrast keratan sulfate was not detected (less than 2 ng/ml) in the serum of 16 patients with histopathologically confirmed MCD. Keratan sulfate was also detected in extracts of normal corneas and corneal tissue with a variety of pathologic conditions, but was virtually absent in corneal tissue from five patients with MCD. In corneas with MCD the chondroitin sulfate/keratan sulfate ratio was considerably higher than that of all normal and pathologic corneas studied. Since keratan sulfate in the serum appears to be derived predominantly from the normal turnover of cartilage these studies strongly suggest that the defect in keratan sulfate synthesis in MCD is not restricted to corneal cells and that MCD is one manifestation of a systemic disorder of keratan sulfate. The cartilage changes, however, do not have clinical significance. Moreover, since keratan sulfate can be detected in the blood of newborns it should be possible to diagnose MCD prior to corneal opacification.
采用一种单克隆抗体（ET-4-A-4）进行酶联免疫吸附测定（ELISA），该抗体可识别I型硫酸角质素（角膜型）和II型硫酸角质素（骨骼型）中的硫酸化碳水化合物表位，以定量检测黄斑角膜营养不良（MCD）患者血清和角膜组织中的硫酸角质素。该测定方法显示，45名健康个体血清中有大量硫酸角质素（251±78 ng/ml），66名患有各种角膜疾病的患者血清中也有大量硫酸角质素（273±101 ng/ml）。相比之下，16名经组织病理学确诊为MCD的患者血清中未检测到硫酸角质素（低于2 ng/ml）。正常角膜和患有各种病理状况的角膜组织提取物中也检测到了硫酸角质素，但5名MCD患者的角膜组织中几乎没有。在患有MCD的角膜中，硫酸软骨素/硫酸角质素的比率明显高于所有研究的正常角膜和病理角膜。由于血清中的硫酸角质素似乎主要来源于软骨的正常更新，这些研究强烈表明，MCD中硫酸角质素合成缺陷并不局限于角膜细胞，MCD是硫酸角质素系统性疾病的一种表现。然而，软骨变化没有临床意义。此外，由于新生儿血液中可检测到硫酸角质素，应该有可能在角膜混浊之前诊断出MCD。
