Proteomic Characterization Reveals That MMP-3 Correlates With Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Cell and Lung Transplantation.
Proteomic Characterization Reveals That MMP-3 Correlates With Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Cell and Lung Transplantation.
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蛋白质组学表征表明，在同种异体造血细胞和肺移植后，MMP-3与细支气管炎综合征相关。
DOI：
10.1111/ajt.13750
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发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Paczesny S
中科院分区：
文献类型：
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作者：
Liu X;Yue Z;Yu J;Daguindau E;Kushekhar K;Zhang Q;Ogata Y;Gafken PR;Inamoto Y;Gracon A;Wilkes DS;Hansen JA;Lee SJ;Chen JY;Paczesny S
闭塞性毛细支气管炎综合征(BOS)是异基因造血细胞移植(HCT)和肺移植后的严重并发症，需要改进诊断方法。在蛋白质候选发现方面，我们比较了来自HCT移植受者的血浆池：发病时BOS(n=12)、肺部感染(n=16)、慢性移植物抗宿主病(n=15)、无肺受累的慢性移植物抗宿主病(n=15)以及HCT后无慢性并发症(n=15)。用不同的标记[相对和绝对量化等压标记(ITRAQ)]和两个软件工具识别差异表达的蛋白质(≥1.5倍变化)。使用六步计算生物学方法进一步选择候选蛋白质。采用酶联免疫吸附试验(EL ISA)检测Hct(n=76)或肺移植(n=36)患者(n=112)血浆中基质金属蛋白酶-3(MMP3)的诊断价值。BOS患者与非BOS患者的血浆MMP3浓度差异有统计学意义(AUC=0.77)。因此，MMP3有可能成为诊断BOS的一种无创血液检测方法。
Improved diagnostic methods are needed for bronchiolitis obliterans syndrome (BOS), a serious complication after allogeneic hematopoietic cell transplantation (HCT) and lung transplantation. For proteins candidate discovery, we compared plasma pools from HCT transplantation recipients with: BOS at onset (n=12), pulmonary infection (n=16), chronic graft-versus-host disease without pulmonary involvement (n=15), and no chronic complications post-HCT (n=15). Pools were labeled with different tags [isobaric Tags for Relative and Absolute Quantification (iTRAQ)], and two software tools identified differentially expressed proteins (≥1.5-fold change). Candidate proteins were further selected using a six-step computational biology approach. The diagnostic value of the lead candidate, matrix metalloproteinase-3 (MMP-3), was evaluated by ELISA in plasma of a verification cohort (n=112) with and without BOS following HCT (n=76) or lung transplantation (n=36). MMP-3 plasma concentrations differed significantly between patients with and without BOS (AUC=0.77). Thus, MMP-3 represents a potential non-invasive blood test for diagnosis of BOS.