HLA-DR expression as a biomarker of inflammation for multicenter clinical trials of ocular surface disease.
HLA-DR expression as a biomarker of inflammation for multicenter clinical trials of ocular surface disease.
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DOI：
10.1016/j.exer.2013.03.018
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发表时间：
2013-06
影响因子：
3.4
通讯作者：
Asbell, Penny A.
中科院分区：
文献类型：
--
作者：
Epstein, Seth P.;Gadaria-Rathod, Neha;Wei, Yi;Maguire, Maureen G.;Asbell, Penny A.
目前还没有经过验证的微创客观指标用于眼表疾病的分类和评估和/或用于评估治疗效果。因此，我们试图建立一个标准化的方法，用于确定眼表炎症生物标志物HLA-DR的相对量，并评估其用于眼表疾病的大型多中心临床试验和转化研究的精度，可靠性和可重复性。进行了多项研究以建立标准操作程序（SOP），用于利用HLA-DR表达作为微创、客观的眼表面炎症生物标志物。已建立的SOP为HLA-DR收集和分析提供了具体的指南，以便将其可靠地纳入多中心临床试验和/或转化研究。收集来自正常和干眼症个体的印迹细胞学（IC）样本的一式两份细胞样本，并将其分开以评估重复性（分开之间和一式两份样本之间）。为了确定储存能力，一个重复样品立即染色，另一个在冷藏30天后染色。为了证明将SOP用于多中心临床试验的可行性，对州外的临床医生进行了培训，以收集IC样本，并将样本运送到我们的生物标志物实验室，进行记录、处理和分析。证明了将IC纳入干眼病（DED）随机双盲临床试验的能力。在所有情况下，由设盲的独立观察员进行处理和分析。通过证明：1）可以通过IC收集足够数量的细胞; 2）样品中定量的相对生物标志物表达的精密度/重复性; 3）可以教导远程研究中心的工作人员成功收集、储存和运输样品; 4）样品可以储存长达30天，确定SOP的有效性/活力在不影响结果的情况下，IC可以在处理之前被冷冻; 5）IC可以被并入DED的双盲随机临床试验（RCT）中;以及6）生物标志物实验室可以可靠地跟踪大量的掩蔽样品。总之，我们用于HLA-DR表达的印迹细胞学分析的标准操作程序似乎是可重复和可再现的，可用于多中心临床试验，提供了眼表炎症的微创客观生物标志物。
There are currently no validated minimally invasive objective metrics for the classification and evaluation of ocular surface diseases and/or for evaluating treatment efficacy. We thus sought to establish a standardized methodology for determining the relative amount of the inflammatory biomarker HLA-DR on the ocular surface and to evaluate the precision, reliability and repeatability of its use for large multicenter clinical trials and translational research studies of ocular surface disease. Multiple studies were conducted to establish a Standard Operating Procedure (SOP) for utilizing HLA-DR expression as a minimally invasive, objective, ocular surface inflammatory biomarker. The established SOPs provide specific guidelines for HLA-DR collection and analysis, in order to incorporate it reliably into multicenter clinical trials and/or translational research. Duplicate cell samples from impression cytology (IC) samples of both normal and dry eye individuals were collected and split to assess repeatability (between the splits and between the duplicate samples). To determine storage capability, one duplicate was stained immediately and the other after 30 days cold storage. To demonstrate the feasibility of the use of the SOP for a multicenter clinical trial, clinicians out-of-state were trained to collect IC samples, and the samples shipped to our Biomarker Laboratory, logged, processed and analyzed. Demonstration of the ability to incorporate of IC into a randomized double masked clinical trial of dry eye disease (DED) was performed. In all cases, processing and analyses were performed by a masked independent observer. The validity/viability of the SOPs was established by demonstrating that: 1) sufficient numbers of cells can be collected via IC; 2) the precision/repeatability of the relative biomarker expression quantified in samples; 3) personnel at distant sites can be taught to collect, store and ship samples successfully; 4) samples can be stored for up to 30 days (refrigeration) before processing without affecting results; 5) IC can be incorporated into a double blind randomized clinical trial (RCT) of DED; and 6) the Biomarker Laboratory can track a large number of masked samples reliably. In conclusion, our standard operating procedure for impression cytology analysis of HLA-DR expression appears to be repeatable and reproducible for use in multicenter clinical trials, providing a minimally invasive objective biomarker of inflammation of the ocular surface.
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影响因子：
4.2
作者：
EGBERT, PR;LAUBER, S;MAURICE, DM
通讯作者：
MAURICE, DM
影响因子：
3.4
作者：
Brignole, F;De Saint-Jean, M;Baudouin, C
通讯作者：
Baudouin, C
影响因子：
--
作者：
GORONZY, JJ;WEYAND, CM
通讯作者：
WEYAND, CM
DOI：
10.1007/s004170000179
发表时间：
2000-11-01
影响因子：
2.7
作者：
Baudouin, C;Bourcier, T;Goguel, A
通讯作者：
Goguel, A
影响因子：
3.4
作者：
Jester, JV;Jin, HC
通讯作者：
Jin, HC