The etiological relation of Epstein-Barr virus to human uveitis

为探讨EB病毒（EBV）与葡萄膜炎的病因学关系，采用聚合酶链反应（PCR）方法检测了不明原因葡萄膜炎患者的血清EBV抗体水平和EBV DNA。我们的研究结果表明，首先，在急性前葡萄膜炎的情况下，传统上被认为是强烈相关的HLA-B27，EBV抗体水平（VCA IgM）升高。然而，这些病例均为HLA B27阴性，因此可能代表一种新认识的葡萄膜炎类型。第二，在某些RPE疾病病例中发现EBV抗体水平和外周EBV感染的淋巴细胞升高，表明与EBV有关。第三，原田病患者脑脊液中发现EBV DNA和EBV抗体。在文献中报道了HLA-DR抗原的第三高变区（其与原田氏病高度相关）与gp 110（存在于被复制性EBV感染的细胞的细胞核和细胞质中的核衣壳糖蛋白）之间的高度氨基酸相关性。我们发现，急性原田氏病患者的淋巴细胞显示增殖反应的肽纳入这个共同的氨基酸序列，从而支持EBV和原田氏病患者之间的特定关联。最后，我们用免疫组织学染色和免疫印迹法（使用OKB 7，一种识别部分EBV受体的单克隆抗体）从正常尸检眼的眼内组织中寻找EBV受体的表达。发现在RPE和部分睫状体中存在EBV受体表达，因此表明EBV直接眼内感染的可能性。

In order to investigate the etiological relationship of Epstein-Barr virus (EBV) to human uveitis, measurement of EBV antibody levels and detection of EBV DNA by the polymerase chain reaction (PCR) method was performed on various samples from patients with uveitis of unknown etiology. Our results showed that first, among cases of acute anterior uveitis, conventionally regarded to be strongly associated with HLA-B27, EBV antibody levels (VCA IgM) were elevated. However, these cases were all negative for HLA B27, and thus may represent a newly recognized type of uveitis. Second, EBV antibody levels and peripheral EBV-infected lymphocytes were found to be elevated in certain cases of RPE disease, suggesting a relationship with EBV. Third, the presence of EBV DNA and EBV antibody was found in the cerebrospinal fluid of patients with Harada's disease. A high amino acid correlation is reported in the literature between the third hypervariable region of the HLA-DR antigen, that is highly associated with Harada's disease, and gp110, the nucleocapsid glycoprotein present in the nucleus and cytoplasm of cells infected with reproducing EBV. We found that lymphocytes from patients with acute Harada's disease display proliferation responses to peptides incorporating this common amino acid sequence, thus lending support to a specific association between EBV and patients with Harada's disease. Lastly, we looked for expression of the EBV receptor in intraocular tissues from normal autopsy eyes with immunohistological stains and western blotting using OKB7,a monoclonal antibody that recognizes part of the EBV receptor. EBV receptor expression was found to be present in the RPE and parts of the ciliary body, therefore indicating the possibility of direct intraocular infection by EBV.