Brignole-Baudouin Françoise, Riancho Luisa, Ismail Dahlia, Deniaud Maëva, Amrane Mourad, Baudouin Christophe
Sorbonne Universités, UPMC Univ Paris 06, Institut de la Vision, Paris, France 2CHNO des Quinze-Vingts, DHU Sight Restore, Paris, France 3Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France.
Sorbonne Universités, UPMC Univ Paris 06, Institut de la Vision, Paris, France.
Invest Ophthalmol Vis Sci. 2017 Apr 1;58(4):2438-2448. doi: 10.1167/iovs.15-16555.
To investigate correlations of the inflammatory HLA-DR marker with clinical signs and symptoms commonly used to assess dry eye disease (DED) severity.
Baseline data were collected from three clinical studies conducted on moderate to severe DED patients. Characteristics of DED were analyzed and correlations were performed in 311 patients. Data were analyzed after treatment with 1 mg/mL cyclosporine (CsA) and vehicle. We quantified HLA-DR by flow cytometry in impression cytology specimens.
We found HLA-DR significantly increased with diagnosis of Sjögren syndrome (P < 0.0001) and meibomian gland disease (P = 0.0223). The strongest significant correlation was seen with the corneal fluorescein staining (CFS, r = 0.30, P < 0.0001). Significant negative relationships were also found with Schirmer's test (r = -0.20, P = 0.0003) and tear break-up time (TBUT, r = -0.13, P = 0.0226). Correlations were statistically significant with total Ocular Surface Disease Index and visual analog scale scores (r = 0.12, P = 0.0426, and r = 0.14, P= 0.0176, respectively). We found HLA-DR arbitrary units of fluorescence were statistically reduced after CsA treatment compared to vehicle (P = 0.022 and P = 0.021 in two studies).
In clinical research on DED, discrepancy is often observed between symptoms and signs. We found HLA-DR correlated significantly with CFS clinical signs and to a lower extent Schirmer's test and weakly with TBUT and symptom reporting questionnaires. HLA-DR was reported to be useful for monitoring anti-inflammatory efficacy treatments in DED, which was confirmed with the reduction of HLA-DR while on CsA treatment. Its expression by conjunctival cells has the potential to serve as a biomarker, bridging signs and symptoms in clinical research in DED, but there is still a need for additional validation studies.
研究炎症性人类白细胞抗原-DR（HLA-DR）标志物与常用于评估干眼病（DED）严重程度的临床体征和症状之间的相关性。
收集了对中度至重度DED患者进行的三项临床研究的基线数据。分析了DED的特征，并在311例患者中进行了相关性分析。在用1mg/mL环孢素（CsA）和赋形剂治疗后对数据进行了分析。我们通过流式细胞术对印迹细胞学标本中的HLA-DR进行了定量。
我们发现HLA-DR在干燥综合征（P < 0.0001）和睑板腺疾病（P = 0.0223）诊断时显著升高。与角膜荧光素染色（CFS，r = 0.30，P < 0.0001）的相关性最强且具有显著性。与泪液分泌试验（r = -0.20，P = 0.0003）和泪膜破裂时间（TBUT，r = -0.13，P = 0.0226）也存在显著负相关。与总眼表疾病指数和视觉模拟量表评分的相关性具有统计学意义（分别为r = 0.12，P = 0.0426和r = 0.14，P = 0.0176）。我们发现与赋形剂相比，CsA治疗后HLA-DR的任意荧光单位在统计学上有所降低（两项研究中P分别为0.022和0.021）。
在DED的临床研究中，症状和体征之间经常存在差异。我们发现HLA-DR与CFS临床体征显著相关，与泪液分泌试验的相关性较低，与TBUT及症状报告问卷的相关性较弱。据报道，HLA-DR有助于监测DED中的抗炎疗效治疗，CsA治疗期间HLA-DR的降低证实了这一点。结膜细胞对其表达有可能作为一种生物标志物，在DED的临床研究中弥合体征和症状，但仍需要更多的验证研究。
