血清KL-6检测在结缔组织病肺间质病变中的意义

A serological biomarker in connective tissue disease-associated interstitial lung disease： Krebs von den lungen-6

目的 研究血清KL-6（Krebs von den lungen-6）作为生物标志物对CTD肺间质病变诊断、影像表现及活动性评估的价值。方法75例CTD患者分为合并肺间质病变组（44例）、不合并肺间质病变组（31例），而合并肺间质病变组再按肺CT影像分型及分级再分别分为3组，按肺间质病变活动与非活动分为2组。以ELISA法测定血清KL-6浓度，数据不服从正态分布，用独立样本非参数检验比较各组间的差异。结果CTD肺间质病变组的血清KL-6浓度[（1 118±877）U/ml]明显高于不合并肺间质病变组[（253±144）U/ml]，差异具有统计学意义（Z=-6.047，P〈0.01）。以500 U/ml为阳性标准，血清KL-6浓度对CTD合并肺间质病变诊断的敏感性、特异性、阳性预测值、阴性预测值分别为72.7%、87.1%、88.9%、69.2%。在合并肺间质病变组的影像分型中，寻常型间质性肺炎（UIP型，蜂窝病变为主）、非特异性间质性肺炎（NSIP型，毛玻璃与网格病变为主）与未定型分组间的血清KL-6浓度[分别为（1 104±843）U/ml、（1 242±1 039）U/ml、（815±400）U/ml]差异无统计学意义（χ2=0.35，P=0.84）。但合并肺间质病变组的影像病变累积分级中，病变分布范围广的患者血清KL-6浓度[（1 910±918）U/ml]较病变分布范围窄组的血清KL-6浓度[（459±268）U/ml]更高（Z=-4.364，P〈0.01）。肺间质病变活动组患者的血清KL-6浓度[（1 478±917）U/ml]也较肺间质病变非活动组[（598±475）U/ml]的高（Z=-3.915，P〈0.01）。结论血清KL-6浓度测定有利于CTD肺间质病变的诊断及肺病变范围及活动度的评估。

Objective To evaluate the serum Krebs von den Lungen （KL）-6 for the diagnosis of interstitial lung disease （ILD） associated with connective tissue diseases （CTD） and its lung-CT subtypes.Methods Seventy-five CTD patients were employed for this study, 44 CTD with ILD and 31 ILD without ILD. The 44 CTD patients with ILD were further divided into different subgroups based on lung-CT imaging and clinical indexes. The enzyme-linked immune sorbent assay （ELISA） was used to measure the serum KL-6 level. For those data that was abnormally distributed, the differences between groups was compared with independent samples nonparametric tests.Results The level of serum KL-6 in the CTD with ILD was significantly higher than that without ILD [（1 118±877） U/ml vs （253±144） U/ml] （Z=-6.047, P〈0.01）. By using a criterion of 500 U/ml, our data suggested that the serum KL-6 level was useful for the ILD-CTD diagnosis; the sensitivity, specificity, positive and negative predictive values were 72.7%, 87.1%, 88.9% and 69.2%, respectively. The serum KL-6 level, however, showed no statistical differences between ILD subtypes, i.e., usual interstitial pneumonia （UIP）, nonspecific interstitial pneumonia （NSIP） and indeterminate [（1 104±843） U/ml, （1 242±1 039） U/ml, （815±400） U/ml, respectively] （χ2=0.35, P=0.84）. Our data further showed that the KL-6 level was significantly higher in CTD-ILD patients with intensive lung lesions than those with limited lung lesions [（1 910±918） U/ml vs （459±268） U/ml] （Z=-4.364, P〈0.01）. In addition, the KL-6 level was significantly higher in active ILDs than in inactive ILDs[（1 478±917） U/ml vs （598±475） U/ml] （Z=-3.915, P〈0.01）.Conclusion The serum KL-6 is a valuable biomarker for CTD-ILD diagnosis and even for the assessment of the extent and activity of lung damage.