Weivoda Starchild, Andersen John D, Skogen Aunica, Schlievert Patrick M, Fontana Donna, Schacker Timothy, Tuite Paul, Dubinsky Janet M, Jemmerson Ronald
Department of Microbiology and Center for Immunology, University of Minnesota, MN 55455, United States.
J Immunol Methods. 2008 Jul 20;336(1):22-9. doi: 10.1016/j.jim.2008.03.004. Epub 2008 Apr 4.
Leucine-rich alpha-2-glycoprotein-1 (LRG) is a serum glycoprotein of unknown function that has shown promise based on qualitative assessments as a biomarker for certain diseases including microbial infections and cancer. However, the lack of a quantitative assay for LRG has limited its application. Here an indirect enzyme-linked immunosorbent assay (ELISA) for quantifying LRG in human serum is described in which cytochrome c is employed as the capturing ligand and a monoclonal antibody specific for LRG is used to detect the captured glycoprotein. Application of this assay in quantifying LRG in various patients' sera is demonstrated. The concentration of LRG in sera of control subjects as determined by this assay is approximately 50 microg/ml. Consistent with expectations from published reports, LRG was found to be significantly elevated in the sera of some patients with a bacterial infection (toxic shock syndrome, TSS). LRG was only slightly elevated in patients infected with the human immunodeficiency virus as compared to uninfected control subjects, while normal levels of LRG were observed in patients with non-infectious diseases (inflammatory arthritis and neurological disorders, primarily Parkinson's disease). Although LRG and C-reactive protein (CRP) are both produced by the liver and are classified as acute-phase proteins, there was no significant correlation between the levels of LRG and CRP in the sera of the patients. Thus, LRG and CRP measurements are non-redundant and indicate different physiological contexts. The ELISA described in this report should be useful to further assess serum LRG as a biomarker for clinical diagnostics.
富含亮氨酸的α-2-糖蛋白-1(LRG)是一种功能未知的血清糖蛋白,基于定性评估,它有望成为包括微生物感染和癌症在内的某些疾病的生物标志物。然而,缺乏对LRG的定量检测方法限制了其应用。本文描述了一种用于定量检测人血清中LRG的间接酶联免疫吸附测定(ELISA)方法,其中细胞色素c用作捕获配体,一种针对LRG的单克隆抗体用于检测捕获的糖蛋白。展示了该检测方法在定量检测各种患者血清中LRG的应用。通过该检测方法测定的对照受试者血清中LRG的浓度约为50微克/毫升。与已发表报告的预期一致,发现一些细菌感染患者(中毒性休克综合征,TSS)的血清中LRG显著升高。与未感染的对照受试者相比,感染人类免疫缺陷病毒的患者血清中LRG仅略有升高,而在患有非感染性疾病(炎症性关节炎和神经系统疾病,主要是帕金森病)的患者中观察到LRG水平正常。虽然LRG和C反应蛋白(CRP)均由肝脏产生且都归类为急性期蛋白,但患者血清中LRG和CRP的水平之间没有显著相关性。因此,LRG和CRP的检测并非冗余,而是指示不同的生理背景。本报告中描述的ELISA方法应有助于进一步评估血清LRG作为临床诊断生物标志物的作用。