Proteomics of Tear Fluid in Thyroid-Associated Orbitopathy
Proteomics of Tear Fluid in Thyroid-Associated Orbitopathy
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甲状腺相关眼病患者泪液的蛋白质组学研究
DOI：
10.1089/thy.2012.0119
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发表时间：
2012-10-01
期刊：
影响因子：
6.6
通讯作者：
Kahaly, George J.
中科院分区：
文献类型：
--
作者：
Matheis, Nina;Okrojek, Rainer;Kahaly, George J.
背景：蛋白质组学和质谱是体液中肽筛选的有用工具。在甲状腺相关性眼眶病（TAO）中，已有报道泪腺受累伴泪液成分改变的证据。我们的目的是检测和评估潜在的变化，泪液蛋白质组模式TAO.Methods：泪液收集45例TAO和15名健康对照。使用表面增强激光解吸/电离飞行时间质谱分析泪液蛋白，并使用基质辅助激光解吸/电离飞行时间技术鉴定肽。分子量3808道尔顿的肽与对照组相比，TAO患者中分别为3734 Da（p = 0.004）、3734 Da（p = 0.034）和3837 Da（p = 0.042）下调。它们被鉴定为富含脯氨酸蛋白4（PRP 4）或其变体鼻咽癌相关PRP 4。3837 Da肽与基础分泌试验呈正相关（r = 0.506，p < 0.001），与临床活动评分（r =-0.334，p < 0.05）和年龄（r =-0.431，p < 0.001）呈负相关。此外，12，003-Da肽在患者中下调（p = 0.019），并被鉴定为β（2）-微球蛋白。随着TAO临床严重程度的增加，泪液中的这种肽减少（p = 0.027）。相比之下，5815-Da肽被上调（p = 0.045），并被鉴定为溶菌酶C。当区分治疗和未治疗的患者与TAO，一个11,770-Da肽（p = 0.0072），也上调被确定为胱抑素S。结论：改变调节的促炎性和保护性蛋白质与TAO患者的眼泪被证明，反映了自身免疫性和/或炎症诱导的泪腺功能障碍。
Background: Proteomics and mass spectrometry are useful tools for peptide screening in body fluids. In thyroid-associated orbitopathy (TAO), evidence for lacrimal gland involvement with altered composition of tears has been reported. Our objective was to detect and evaluate potential changes in the proteomic patterns of tear fluid in TAO.Methods: Tear fluid was collected from 45 patients with TAO and 15 healthy controls. Tear proteins were analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, and peptides were identified using matrix-assisted laser desorption/ionization time-of-flight technology.Results: Peptides with molecular weights 3808 Dalton (Da, p = 0.004), 3734 Da (p = 0.034), and 3837 Da (p = 0.042), respectively, were downregulated in patients with TAO versus controls. They were identified as proline-rich protein 4 (PRP4) or as its variant nasopharyngeal carcinoma-associated PRP4. The peptide 3837 Da correlated positively with the basal secretory test (r = 0.506, p < 0.001) and negatively with the clinical activity score (r = -0.334, p < 0.05) and age (r = -0.431, p < 0.001). Also, a 12,003-Da peptide was downregulated (p = 0.019) in patients and identified as beta(2)-microglobulin. This peptide decreased in tear fluid with increased clinical severity of TAO (p = 0.027). In comparison, a 5815-Da peptidewas upregulated (p = 0.045) and identified as lysozyme C. When differentiating between treated and untreated patients with TAO, an 11,770-Da peptide (p = 0.0072) that was also upregulated was identified as cystatin S.Conclusions: Altered regulation of proinflammatory and protective proteins in tears of patients with TAO was demonstrated, reflecting an autoimmune- and/or inflammatory-induced dysfunction of the lacrimal gland.