Oetting William S, Rogers Tyson B, Krick Thomas P, Matas Arthur J, Ibrahim Hassan N
Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Am J Kidney Dis. 2006 May;47(5):898-904. doi: 10.1053/j.ajkd.2006.01.034.
Identifying urinary biomarkers associated with acute rejection (AR) of kidney allografts could improve recipient care by allowing AR to be diagnosed noninvasively and treated earlier. We attempted to identify novel biomarkers associated with AR by analyzing urinary proteins by using matrix-associated laser desorption ionization time-of-flight mass spectroscopy (MALDI-TOF MS).
Using MALDI-TOF MS, we analyzed urine samples from 30 renal allograft recipients with biopsy-proven AR, 15 allograft recipients without AR, preoperative samples from 29 kidney donors, and 10 subjects with proteinuric native kidney disease.
In samples obtained at the time of AR, we identified a protein peak at 11.7 kd that correlated strongly with AR. In regard to its predictive power for AR, this protein peak showed sensitivity of 83.3%, specificity of 80%, positive predictive value of 89%, and negative predictive value of 70.6%, suggesting that this protein is highly associated with AR. We identified this peak as being beta2-microglobulin. This was validated by using enzyme-linked immunosorbent assay, which documented the presence of high urinary beta2-microglobulin levels in subjects with AR.
Beta2-microglobulin could be a strong biomarker for AR if used in conjunction with other biomarkers, producing an AR-specific urinary protein signature. This possibility must be confirmed in a larger cohort of kidney transplant recipients.
通过无创诊断和早期治疗急性排斥反应(AR)来改善肾移植受者的护理,识别与肾移植急性排斥反应相关的尿液生物标志物。我们试图通过使用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)分析尿液蛋白质来识别与AR相关的新型生物标志物。
使用MALDI-TOF MS,我们分析了30例经活检证实为AR的肾移植受者、15例无AR的移植受者、29例肾供者的术前样本以及10例患有蛋白尿性肾病的受试者的尿液样本。
在急性排斥反应时获得的样本中,我们在11.7 kd处鉴定出一个与AR密切相关的蛋白峰。就其对AR的预测能力而言,该蛋白峰的敏感性为83.3%,特异性为80%,阳性预测值为89%,阴性预测值为70.6%,表明该蛋白与AR高度相关。我们将该峰鉴定为β2-微球蛋白。通过酶联免疫吸附测定法进行了验证,该方法记录了AR受试者尿液中β2-微球蛋白水平较高。
如果与其他生物标志物联合使用,β2-微球蛋白可能是AR的一个强有力的生物标志物,产生AR特异性尿液蛋白特征。这种可能性必须在更大的肾移植受者队列中得到证实。