Conjunctival Inflammatory Gene Expression Profiling in Dry Eye Disease: Correlations With HLA-DRA and HLA-DRB1.
Conjunctival Inflammatory Gene Expression Profiling in Dry Eye Disease: Correlations With HLA-DRA and HLA-DRB1.
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DOI：
10.3389/fimmu.2018.02271
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发表时间：
2018
影响因子：
7.3
通讯作者：
Brignole-Baudouin F
中科院分区：
文献类型：
--
作者：
Kessal K;Liang H;Rabut G;Daull P;Garrigue JS;Docquier M;Melik Parsadaniantz S;Baudouin C;Brignole-Baudouin F
目的：在多个多中心临床试验中，人类白细胞抗原-DR被发现是预测S干眼病病情严重程度和预后的潜在生物标志物。鉴于人类白细胞抗原-DR受体是一个由α链和β链组成的异源二聚体，我们打算研究炎症靶点与相应的转录产物--人类白细胞抗原-DRA和人类白细胞抗原-DRB1的相关性，以确定与不同病因的DED患者结膜细胞中表达的人类白细胞抗原-DR密切相关的特异性靶点。方法：对88例不同类型DED患者进行前瞻性研究。观察眼部症状评分、眼部染色分级、泪液破裂时间(TBUT)和Schirmer试验。通过Impression细胞学收集浅结膜细胞，并提取总RNA，用于使用基于包含249个炎症基因的炎症性人类密码组的新的NanoString®nCounter技术进行分析。结果：在结膜组织标本中可靠地检测到200个转录本，其RNA拷贝数从1到222,546个不等。总体而言，在88个样本中，21个靶基因与人类白细胞抗原-DRA呈高度显著相关(R>；0.8)，其中以人类白细胞抗原-DRB1、人类白细胞抗原-DRA和基因B1的相关性最高(R=0.9)。这些靶点分别属于8个家族，即干扰素及干扰素刺激基因、肿瘤坏死因子超家族及相关因子、Toll样受体及相关因子、补体系统因子、趋化因子/细胞因子、RIPK酶家族以及STAT和MAPK家族等信号转导通路。结论：我们已经确定了21个与人类白细胞抗原-DR表达相关的转录本，提示了密切调控的信号通路以及它们之间可能的直接或间接相互作用。结膜印迹中的NanoString®计数器技术可能成为未来在DED中更广泛地筛选炎性生物标记物的可靠工具，适用于非常小的样本。可以分析与人类白细胞抗原-DR相关的更广泛的生物标记物组合，以开发新的诊断方法，识别更紧密的病理生理基因特征，并更有效地个性化DED治疗。
Purpose: In several multicenter clinical trials, HLA-DR was found to be a potential biomarker of dry eye disease (DED)'s severity and prognosis. Given the fact that HLA-DR receptor is a heterodimer consisting in an alpha and a beta chain, we intended to investigate the correlation of inflammatory targets with the corresponding transcripts, HLA-DRA and HLA-DRB1, to characterize specific targets closely related to HLA-DR expressed in conjunctival cells from patients suffering from DED of various etiologies. Methods: A prospective study was conducted in 88 patients with different forms of DED. Ocular symptom scores, ocular-staining grades, tear breakup time (TBUT) and Schirmer test were evaluated. Superficial conjunctival cells were collected by impression cytology and total RNAs were extracted for analyses using the new NanoString® nCounter technology based on an inflammatory human code set containing 249 inflammatory genes. Results: Two hundred transcripts were reliably detected in conjunctival specimens at various levels ranging from 1 to 222,546 RNA copies. Overall, from the 88 samples, 21 target genes showed a highly significant correlation (R > 0.8) with HLA-DRA and HLA-DRB1, HLA-DRA and B1 presenting the highest correlation (R = 0.9). These selected targets belonged to eight family groups, namely interferon and interferon-stimulated genes, tumor necrosis factor superfamily and related factors, Toll-like receptors and related factors, complement system factors, chemokines/cytokines, the RIPK enzyme family, and transduction signals such as the STAT and MAPK families. Conclusions: We have identified a profile of 21 transcripts correlated with HLA-DR expression, suggesting closely regulated signaling pathways and possible direct or indirect interactions between them. The NanoString® nCounter technology in conjunctival imprints could constitute a reliable tool in the future for wider screening of inflammatory biomarkers in DED, usable in very small samples. Broader combinations of biomarkers associated with HLA-DR could be analyzed to develop new diagnostic approaches, identify tighter pathophysiological gene signatures and personalize DED therapies more efficiently.
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影响因子：
4.4
作者：
Chotikavanich S;de Paiva CS;Li de Q;Chen JJ;Bian F;Farley WJ;Pflugfelder SC
通讯作者：
Pflugfelder SC
影响因子：
14.2
作者：
Baudouin, C;Liang, H;Brignole-Baudouin, F
通讯作者：
Brignole-Baudouin, F
DOI：
10.1016/0167-5699(91)90009-i
发表时间：
1991-09-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
FRANK, MM;FRIES, LF
通讯作者：
FRIES, LF
影响因子：
4.4
作者：
Giroux, M;Schmidt, M;Descoteaux, A
通讯作者：
Descoteaux, A
干扰素诱导基因作为系统性红斑狼疮诊断生物标志物的鉴定
影响因子：
3.4
作者：
Feng, Xuebing;Huang, Jing;Sun, Lingyun
通讯作者：
Sun, Lingyun