Proteomic analysis of saliva from patients with oral chronic graft-versus-host disease.
Proteomic analysis of saliva from patients with oral chronic graft-versus-host disease.
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DOI：
10.1016/j.bbmt.2014.03.031
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发表时间：
2014-07
期刊：
影响因子：
--
通讯作者：
Presland RB
中科院分区：
文献类型：
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作者：
Devic I;Shi M;Schubert MM;Lloid M;Izutsu KT;Pan C;Missaghi M;Morton TH;Mancl LA;Zhang J;Presland RB
慢性移植物抗宿主病（cGVHD）是一种免疫介导的疾病，是异基因造血干细胞移植（allo-HSCT）的主要长期并发症。包括唾液腺在内的口腔粘膜在大多数cGVHD患者中受到影响;然而，目前对疾病病理生物学的了解有限。在这项研究中，我们使用iTRAQ（相对和绝对定量的同量异序标签）标记，然后使用串联质谱法对口腔cGVHD（+）和口腔cGVHD（-）患者合并的唾液进行定量蛋白质组学分析。在通过串联质谱鉴定的249种唾液蛋白中，与没有口腔cGVHD的allo-HSCT患者相比，82种蛋白在口腔cGVHD患者中表现出改变的表达。许多鉴定的蛋白质在先天性或获得性免疫中起作用，或者与组织维持功能如蛋白水解或细胞骨架相关。ELISA免疫分析进一步证实了IL-1受体拮抗剂和Cystatin B在活动性cGVHD患者中的表达降低（P < 0.003）。受试者操作者特征分析显示，这两种标记物能够区分口腔cGVHD，灵敏度为85%，特异性为60%，并且在allo-HSCT移植12个月内研究的新诊断患者中显示出略好的区分度（灵敏度，92%;特异性73%）。除了鉴定新的潜在唾液cGVHD生物标志物外，我们的研究表明，口腔cGVHD中涉及炎症，抗微生物防御和组织保护的蛋白质家族存在协调调节，这也可能反映唾液腺功能的变化和口腔粘膜的损伤。
Chronic graft-versus-host disease (cGVHD) is an immune-mediated disorder and is the major long-term complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The oral mucosa including the salivary glands is affected in the majority of cGVHD patients; however, at present there is only a limited understanding of disease pathobiology. In this study, we performed a quantitative proteomic analysis of saliva pooled from oral cGVHD(+) and oral cGVHD(-) patients using iTRAQ (isobaric Tags for Relative and Absolute Quantification) labeling, followed by tandem mass spectrometry. Among 249 salivary proteins identified by tandem mass spectrometry, 82 proteins exhibited altered expression in oral cGVHD patients compared to allo-HSCT patients without oral cGVHD. Many of the identified proteins function in innate or acquired immunity, or are associated with tissue maintenance functions such as proteolysis or the cytoskeleton. Using ELISA immunoassays, we further confirmed that two of these proteins, IL-1 receptor antagonist and Cystatin B, showed decreased expression in patients with active oral cGVHD (P < 0.003). Receiver Operator Characteristic analysis revealed that these two markers were able to distinguish oral cGVHD with a sensitivity of 85% and specificity of 60%, and showed slightly better discrimination in newly diagnosed patients studied within 12 months of allo-HSCT transplantation (sensitivity, 92%; specificity 73%). In addition to identifying novel potential salivary cGVHD biomarkers, our study demonstrates that there is coordinated regulation of protein families involved in inflammation, anti-microbial defense and tissue protection in oral cGVHD that may also reflect changes in salivary gland function and damage to the oral mucosa.