El Kochairi Ilhem, Letovanec Igor, Uffer Sylvie, Munier Francis L, Chaubert Pascal, Schorderet Daniel F
Institut de Recherche en Ophtalmologie, Sion, Switzerland.
Mol Vis. 2006 May 10;12:461-6.
To investigate the location and tissue-specificity of the pathologic keratoepithelin (KE) deposition in a patient with a keratoepithelinopathy (KEP), TGFBI/BIGH3-related corneal dystrophy.
An autopsy was performed in a patient with lattice type I corneal dystrophy (LCDI) after authorization was obtained from the family. Mutation screening in TGFBI/BIGH3 was done on the patient several years ago. Eighteen different tissues or organs, including brain, heart, lung, kidney, liver, lymph nodes, spleen, aorta, esophagus, bone marrow, urinary bladder (including a papillary urothelial carcinoma), samples of a metastatic squamous cell carcinoma, adrenal gland, parathyroid gland, muscle, prostate, and cornea were investigated, and sections from the tissues were labeled with KE2 rabbit TGFBI/BIGH3 antiserum.
The patient, diagnosed with LCDI and Alzheimer's disease, died at 79 years of age from a complicated chronic obstructive lung disease. Mutation analysis showed the classical Arg124Cys mutation in exon 4 of TGFBI/BIGH3, associated with LCDI. Except for the cornea, immunostaining with KE2 antisera did not reveal any deposits in any of the 17 other organs analyzed.
Pathologic deposits caused by KE accumulation were only observed in the cornea and in no other tissue or organ in this patient. These results suggest a cornea-specific mechanism in the aggregation of KE. Further studies need to be done to investigate whether the degradation of mutated KE generates cornea-specific fragments that aggregate or whether the clearing of normal fragments is different in affected corneas, which then leads to aggregation.
研究角膜上皮素病（KEP）（一种与转化生长因子β诱导蛋白（TGFBI）/富含亮氨酸重复序列免疫球蛋白超家族成员3（BIGH3）相关的角膜营养不良）患者中病理性角膜上皮素（KE）沉积的位置和组织特异性。
在获得患者家属授权后，对一名患有I型格子状角膜营养不良（LCDI）的患者进行尸检。几年前对该患者进行了TGFBI/BIGH3的突变筛查。研究了18种不同的组织或器官，包括脑、心脏、肺、肾脏、肝脏、淋巴结、脾脏、主动脉、食管、骨髓、膀胱（包括乳头状尿路上皮癌）、转移性鳞状细胞癌样本、肾上腺、甲状旁腺、肌肉、前列腺和角膜，并用KE2兔抗TGFBI/BIGH3抗血清对这些组织的切片进行标记。
该患者被诊断为LCDI和阿尔茨海默病，79岁时死于复杂的慢性阻塞性肺疾病。突变分析显示TGFBI/BIGH3第4外显子存在经典的Arg124Cys突变，与LCDI相关。除角膜外，用KE2抗血清进行免疫染色未在分析的其他17个器官中发现任何沉积物。
在该患者中，仅在角膜中观察到由KE积累引起的病理性沉积物，在其他组织或器官中未观察到。这些结果提示KE聚集存在角膜特异性机制。需要进一步研究来探讨突变KE的降解是否产生聚集的角膜特异性片段，或者受影响角膜中正常片段的清除是否不同，进而导致聚集。
