Multiplex bead immunoassay analysis of aqueous humor reveals distinct cytokine profiles in uveitis
Multiplex bead immunoassay analysis of aqueous humor reveals distinct cytokine profiles in uveitis
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DOI：
10.1167/iovs.05-0444
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发表时间：
2005-11-01
影响因子：
4.4
通讯作者：
Murray, PI
中科院分区：
文献类型：
--
作者：
Curnow, SJ;Falciani, F;Murray, PI
目的.目的探讨葡萄膜炎房水（AqH）中细胞因子的复杂网络及其与细胞浸润的关系。对来自非炎症对照受试者和患有特发性、Fuchs异色性睫状体炎（FHC）和疱疹病毒性或Behcet葡萄膜炎的患者的AqH分析IL-1 β、-2、-4、-5、-7、-8、-10、-12、-13、-15、TNF α、IFN γ、CCL 2（MCP-1）、CCL 5（RANTES）、CCL 11（嗜酸性粒细胞趋化因子）、TGF β 2、和CXCL 12（SDF-1）。还测定了每个样品的细胞浸润。与非炎症对照组相比，特发性葡萄膜炎AqH的特征在于高水平的IL-6、IL-8、CCL 2和IFN γ，这些水平彼此相关。对于IL-6和IL-8，这些水平与存在的中性粒细胞数量成比例。相比之下，TGF β 2和CXCL 12的水平在特发性葡萄膜炎AqH中随着炎症的增加而降低。聚类分析显示非炎症性和特发性葡萄膜炎AqH之间存在一定程度的分离。使用随机森林分析的进一步检查在这两组之间产生了完全的区别。该分类所需的最低细胞因子为IL-6、IL-8、CCL 2、IL-13、TNF α和IL-2。多重珠免疫分析的应用，使我们能够确定不同的模式的细胞因子，涉及临床疾病和细胞浸润。生物信息学分析允许识别区分特发性葡萄膜炎与非炎症对照AqH的细胞因子，并且可能对葡萄膜炎的发病机制很重要。
PURPOSE. To extensively characterize the complex network of cytokines present in uveitis aqueous humor (AqH), and the relationships between cytokines and the cellular infiltrate.METHODS. AqH from noninflammatory control subjects and patients with idiopathic, Fuchs' heterochromic cyclitis (FHC), and herpes-viral or Behcet's uveitis were analyzed for IL-1 beta, -2, - 4, - 5, - 7, - 8, - 10, - 12, - 13, - 15, TNF alpha, IFN gamma, CCL2 (MCP-1), CCL5 (RANTES), CCL11 (Eotaxin), TGF beta 2, and CXCL12 (SDF-1), using multiplex bead immunoassays. The cellular infiltrate was also determined for each sample.RESULTS. Idiopathic uveitis AqH, compared with noninflammatory controls, was characterized by high levels of IL-6, IL-8, CCL2 and IFN gamma, the levels of which correlated with each other. For IL-6 and IL-8 these levels were proportional to the number of neutrophils present. By contrast, the levels of both TGF beta 2 and CXCL12 decreased in idiopathic uveitis AqH with increasing inflammation. Cluster analysis showed a degree of segregation between noninflammatory and idiopathic uveitis AqH. Further examination using random forest analysis yielded a complete distinction between these two groups. The minimum cytokines required for this classification were IL-6, IL-8, CCL2, IL-13, TNF alpha, and IL-2.CONCLUSIONS. Application of multiplex bead immunoassays has allowed us to identify distinct patterns of cytokines that relate to both clinical disease and the cellular infiltrates present. Bioinformatics analysis allowed identification of cytokines that differentiate idiopathic uveitis from noninflammatory control AqH and are likely to be important for the pathogenesis of uveitis.