Urinary β2-microglobulin is associated with acute renal allograft rejection
Urinary β2-microglobulin is associated with acute renal allograft rejection
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DOI：
10.1053/j.ajkd.2006.01.034
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发表时间：
2006-05-01
影响因子：
13.2
通讯作者：
Ibrahim, Hassan N.
中科院分区：
文献类型：
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作者：
Oetting, William S.;Rogers, Tyson B.;Ibrahim, Hassan N.
背景：识别与移植肾急性排斥反应(AR)相关的尿液生物标志物可以使AR得到无创的诊断和早期治疗，从而改善受者的护理。我们试图通过使用基质相关激光解吸电离飞行时间质谱仪(MALDI-TOF MS)分析尿蛋白来识别与AR相关的新的生物标记物。方法应用MALDI-TOF MS分析30例经活检证实为AR的同种异体肾移植受者、15例无AR的同种异体肾移植受者的尿样，29例肾供者的术前尿样，以及10例蛋白尿性天然肾病患者的尿样。结果：在AR时获得的样品中，我们在11.7kd处发现了一个与AR密切相关的蛋白质峰。该蛋白峰预测AR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%，提示该蛋白与AR密切相关。我们确定这个峰是β(2)-微球蛋白。用酶联免疫吸附试验证实了这一点，该试验记录了AR受试者存在高尿β(2)-微球蛋白水平。结论：如果与其他生物标志物联合使用，β(2)-微球蛋白可以成为AR的一个强有力的生物标志物，产生AR特异的尿蛋白信号。这种可能性必须在更大的肾移植受者队列中得到证实。
Background: 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). Methods 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. Results: 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 beta(2)-microglobulin. This was validated by using enzyme-linked immunosorbent assay, which documented the presence of high urinary beta(2)-microglobulin levels in subjects with AR. Conclusion: beta(2)-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.