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[干燥性角结膜炎时印迹细胞学中的流式细胞术:局部应用环孢素A对HLA DR表达的影响]

[Flow cytometry in impression cytology during keratoconjunctivitis sicca: effects of topical cyclosporin A on HLA DR expression].

作者信息

Galatoire O, Baudouin C, Pisella P J, Brignole F

机构信息

Service d'Ophtalmologie 3, Hôpital des Quinze-Vingts, 28, rue de Charenton, 75012 Paris.

出版信息

J Fr Ophtalmol. 2003 Apr;26(4):337-43.

Abstract

PURPOSE

Immune-based inflammation has been observed as a common mechanism of keratoconjunctivitis sicca (KCS). In KCS-affected eyes, up-regulated expression of HLA DR by conjunctival epithelial cells has been demonstrated in impression cytology (IC) specimens using a technique of flow cytometry. The purpose of this study was to monitor the effects of topical cyclosporin A on the expression of this marker over a 12-month period of treatment.

METHODS

Patients with moderate-to-severe KCS included in a large European multicenter clinical trial (Cyclosporin Dry Eye Study, Allergan, Irvine, CA) underwent collection of IC specimens at baseline, month 3, month 6, and month 12. They randomly received 0.05% or 0.1% cyclosporin A or vehicle. Patients randomized to receive vehicle received 0.1% cyclosporin A from month 6 onwards. Specimens were processed and analyzed in a masked manner by flow cytometry, using monoclonal antibodies directed to HLA DR.

RESULTS

We included 169 patients in this study. HLA DR expression, both in percentage of positive cells and level of expression, was highly significantly reduced after 0.05% and 0.1% cyclosporin A treatment at months 3, 6, and 12 compared with baseline values, whereas vehicle did not induce any change in HLA DR expression over time. The 0.05% and 0.1% cyclosporin emulsions were significantly more effective than the vehicle in reducing HLA DR at months 3 and 6 (0.05%) and at month 6 (0.1%).

CONCLUSIONS

Topical cyclosporin A strikingly reduced HLA DR, whereas the vehicle, used as a control tear substitute, had almost no effect. This study confirms that cyclosporin A may be effective in reducing conjunctival inflammation in moderate-to-severe KCS and is consistent with clinical results in this indication.

摘要

目的

基于免疫的炎症已被视作干燥性角结膜炎(KCS)的常见机制。在受KCS影响的眼睛中,采用流式细胞术技术在印片细胞学(IC)标本中已证实结膜上皮细胞的HLA DR表达上调。本研究的目的是监测局部应用环孢素A在12个月治疗期间对该标志物表达的影响。

方法

纳入一项大型欧洲多中心临床试验(环孢素干眼研究,Allergan公司,加利福尼亚州欧文市)的中重度KCS患者在基线、第3个月、第6个月和第12个月接受IC标本采集。他们随机接受0.05%或0.1%环孢素A或赋形剂。随机接受赋形剂的患者从第6个月起接受0.1%环孢素A。标本采用针对HLA DR的单克隆抗体,通过流式细胞术以盲法进行处理和分析。

结果

本研究纳入了169例患者。与基线值相比,在第3、6和12个月,0.05%和0.1%环孢素A治疗后,HLA DR表达在阳性细胞百分比和表达水平方面均显著降低,而赋形剂随时间未引起HLA DR表达的任何变化。在第3个月和第6个月(0.05%)以及第6个月(0.1%),0.05%和0.1%环孢素乳剂在降低HLA DR方面显著优于赋形剂。

结论

局部应用环孢素A显著降低了HLA DR,而用作对照泪液替代品的赋形剂几乎没有效果。本研究证实环孢素A可能有效减轻中重度KCS的结膜炎症,并且与该适应证的临床结果一致。

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