Pappa A, Calder V, Fells P, Lightman S
Moorfields Eye Hospital NHS Trust and Department of Clinical Ophthalmology, Institute of Ophthalmology, London, UK.
Clin Exp Immunol. 1997 May;108(2):309-13. doi: 10.1046/j.1365-2249.1997.3621258.x.
TAO is an autoimmune condition characterized by mononuclear cell infiltration of the extraocular muscles (EOM) and/or the orbital fat/connective tissue with associated deposition of glycosaminoglycans (GAG) in the interstitial spaces. In this study, the presence and distribution of the vascular adhesion molecules intercellular adhesion molecule-1 (ICAM-1), endothelial-leucocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1) and the leucocyte integrins CD11a/CD18, CD11b/CD18, CD11c/CD18 were investigated. Nineteen EOM biopsies were collected from 17 patients with early (n = 6) and late (n = 13) TAO as well as from 12 non-TAO control patients. Consecutive cryostat sections of these biopsies were immunostained with MoAbs to the above-mentioned molecules and haematoxylin and eosin. Primary antibody binding was visualized using an avidin-biotin system. In early untreated TAO specimens, the interstitial and perimysial connective tissue surrounding EOM fibres and numerous mononuclear cells stained strongly for ICAM-1. In contrast, the vascular endothelial cells (ulex lectin-positive) stained strongly for ELAM-1 (E-selectin), VCAM-1 as well as ICAM-1. In late disease, the same distribution of immunoreactivity for ICAM-1, ELAM-1 and VCAM-1 was observed, but with significantly lower staining. The leucocyte integrins (CD11a, CD11b, CD11c) were again expressed at significantly higher levels in early TAO specimens compared with late TAO specimens and were minimal or absent in the EOM biopsies harvested from control patients. In conclusion, increased expression of adhesion molecules studied correlated with early active disease and was reduced in later stages.
甲状腺相关眼病(TAO)是一种自身免疫性疾病,其特征为眼外肌(EOM)和/或眼眶脂肪/结缔组织有单核细胞浸润,且间质间隙有糖胺聚糖(GAG)沉积。在本研究中,调查了血管黏附分子细胞间黏附分子-1(ICAM-1)、内皮白细胞黏附分子-1(ELAM-1)、血管细胞黏附分子-1(VCAM-1)以及白细胞整合素CD11a/CD18、CD11b/CD18、CD11c/CD18的存在及分布情况。从17例早期(n = 6)和晚期(n = 13)TAO患者以及12例非TAO对照患者身上采集了19份EOM活检样本。这些活检样本的连续冰冻切片用针对上述分子的单克隆抗体以及苏木精和伊红进行免疫染色。使用抗生物素蛋白-生物素系统观察一抗结合情况。在未经治疗的早期TAO样本中,EOM纤维周围的间质和肌周结缔组织以及众多单核细胞对ICAM-1染色强烈。相比之下,血管内皮细胞(荆豆凝集素阳性)对ELAM-1(E-选择素)、VCAM-1以及ICAM-1染色强烈。在疾病晚期,观察到ICAM-1、ELAM-1和VCAM-1的免疫反应性分布相同,但染色明显减弱。与晚期TAO样本相比,白细胞整合素(CD11a、CD11b、CD11c)在早期TAO样本中的表达水平再次显著更高,而在对照患者的EOM活检样本中表达极少或无表达。总之,所研究的黏附分子表达增加与早期活动性疾病相关,而在后期阶段则减少。