Eberwein Philipp, Issleib Susanne, Böhringer Daniel, Mittelviefhaus Hans, Schwartzkopff Johannes, Finke Juergen, Reinhard Thomas
University Eye Hospital, Albert-Ludwig-University, Freiburg, Germany.
Mol Vis. 2013 Jul 19;19:1492-501. Print 2013.
To assess the expression of human leucocyte antigen (HLA)-DR in epithelial cells and cluster of differentiation (CD8)-positive lymphocytes as possible markers of chronic ocular graft versus host disease (cGvHD) after hematological stem cell transplantation (HSCT).
Twenty-seven consecutive patients with dry-eye symptoms following HSCT (24 [89%] with peripheral blood stem cell transplantation and 3 [11%] with bone marrow transplants; 17 [63%] familiar allogenic grafts) and 19 age-matched controls were included. Conjunctival impression cytology specimens were stained for HLA-DR, cytokeratin 19, and CD8. Oxford grading scale, blinking frequency, Schirmer test, tear film break-up time (TBUT), and Ocular Surface Disease Index (OSDI) were also recorded. Wilcoxon nonparametric testing was used to compare controls and HSCT recipients and to assess HSCT recipient subgroups with and without clinical cGVHD.
Eighteen patients showed clinical signs of ocular cGVHD. TBUT and Schirmer test scores were significantly lower in patients, while Oxford grades and OSDI were significantly higher than in controls. Epithelial HLA-DR expression was generally higher in HSCT recipients than in controls, but it did not correlate with ocular cGVHD status. CD8-positive lymphocytes were identified in five patients with ocular cGvHD and one control.
A strong HLA-DR expression as detected by impression cytology appears to indicate a general HSCT response and fails to predict ocular cGVHD. However, the detection of CD8-positive lymphocytes using impression cytology was frequently associated with ocular cGvHD. Our data warrant further evaluation of CD8 expression in impression cytology, along with comparison to conjunctival biopsies and brush cytology, as impression cytology may offer a less invasive strategy for assessing cGVHD status.
评估人类白细胞抗原(HLA)-DR在上皮细胞和分化簇(CD8)阳性淋巴细胞中的表达,作为血液干细胞移植(HSCT)后慢性眼部移植物抗宿主病(cGvHD)的潜在标志物。
纳入27例HSCT后出现干眼症状的连续患者(24例[89%]接受外周血干细胞移植,3例[11%]接受骨髓移植;17例[63%]为亲缘同种异体移植)以及19例年龄匹配的对照。对结膜印片细胞学标本进行HLA-DR、细胞角蛋白19和CD8染色。记录牛津分级量表、眨眼频率、泪液分泌试验、泪膜破裂时间(TBUT)和眼表疾病指数(OSDI)。采用Wilcoxon非参数检验比较对照组和HSCT受者,并评估有或无临床cGVHD的HSCT受者亚组。
18例患者表现出眼部cGVHD的临床体征。患者的TBUT和泪液分泌试验评分显著低于对照组,而牛津分级和OSDI显著高于对照组。HSCT受者上皮HLA-DR表达总体上高于对照组,但与眼部cGVHD状态无关。在5例眼部cGvHD患者和1例对照中发现了CD8阳性淋巴细胞。
印片细胞学检测到的强烈HLA-DR表达似乎表明HSCT的一般反应,无法预测眼部cGVHD。然而,使用印片细胞学检测到的CD8阳性淋巴细胞常与眼部cGvHD相关。我们的数据值得进一步评估印片细胞学中CD8的表达,并与结膜活检和刷片细胞学进行比较,因为印片细胞学可能为评估cGVHD状态提供一种侵入性较小的策略。