Fox R I, Luppi M, Kang H I, Pisa P
Department of Rheumatology and Immunology, Scripps Clinic and Research Foundation, La Jolla, CA 92037.
Springer Semin Immunopathol. 1991;13(2):217-31. doi: 10.1007/BF00201470.
Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by severe dryness of the eyes and mouth, resulting from lymphocytic infiltration of the lacrimal and salivary glands. SS may exist as a primary condition (primary SS, 1.SS) or as a secondary condition (2.SS) in association with rheumatoid arthritis, systemic lupus erythematosus, or progressive systemic sclerosis. In some 1.SS patients, there may be involvement of the extraglandular organs, including skin, kidney, liver, lung and nervous system. Furthermore, these patients may develop a lymphoproliferative syndrome that includes lymphadenopathy and increased risk of lymphoma. In the pathogenesis of SS, a role for Epstein-Barr virus (EBV) has been suggested because: (a) EBV is present in salivary gland epithelial cells of normal individuals and exaggerated immune responses against EBV could play a role in the destruction of salivary glands in SS; (b) SS salivary gland biopsies contain increased levels of EBV DNA in comparison to normal salivary glands, indicating viral reactivation and inability of lymphoid infiltrates to control EBV replication in SS patients; and (c) salivary gland epithelial cells in SS patients express high levels of HLA-DR antigens and may present EBV-associated antigens to immune T cells in SS patients. Therefore, SS may represent a situation in which genetically predisposed individuals (i.e., HLA-DR3-DQA4-DQB2) have a persistent but ineffectual T cell immune response against EBV at its site of latency. Among 14 non-Hodgkin's lymphomas that developed in SS patients, EBV DNA was detected in increased amounts in the tumor tissue of one patient. Characterization of this tumor DNA revealed: (a) polyclonal immunoglobulin gene rearrangements; (b) EBV DNA with an unusual restriction fragment length polymorphism pattern involving the Bam M fragment; and (c) EBV terminal repeat sequences suggestive of viral replication, similar to those reported in EBV lymphomas occurring in other immunocompromised individuals. Early recognition of this clinical problem may allow beneficial use of antiviral agents.
干燥综合征（SS）是一种慢性自身免疫性疾病，其特征为眼干和口干严重，由泪腺和唾液腺的淋巴细胞浸润所致。SS可作为原发性疾病（原发性SS，pSS）存在，或作为继发性疾病（继发性SS，sSS）与类风湿关节炎、系统性红斑狼疮或进行性系统性硬化症相关联。在一些pSS患者中，可能会累及腺外器官，包括皮肤、肾脏、肝脏、肺和神经系统。此外，这些患者可能会发展为淋巴增殖综合征，包括淋巴结病和淋巴瘤风险增加。在SS的发病机制中，有人提出爱泼斯坦-巴尔病毒（EBV）发挥了作用，原因如下：（a）EBV存在于正常个体的唾液腺上皮细胞中，针对EBV的过度免疫反应可能在SS唾液腺破坏中起作用；（b）与正常唾液腺相比，SS唾液腺活检中EBV DNA水平升高，表明病毒再激活以及淋巴细胞浸润无法控制SS患者体内的EBV复制；（c）SS患者的唾液腺上皮细胞表达高水平的HLA-DR抗原，可能将EBV相关抗原呈递给SS患者的免疫T细胞。因此，SS可能代表一种情况，即遗传易感性个体（即HLA-DR3-DQA4-DQB2）在EBV潜伏部位对其产生持续但无效的T细胞免疫反应。在SS患者发生的14例非霍奇金淋巴瘤中，在1例患者的肿瘤组织中检测到EBV DNA含量增加。对该肿瘤DNA的特征分析显示：（a）多克隆免疫球蛋白基因重排；（b）EBV DNA具有涉及Bam M片段的异常限制性片段长度多态性模式；（c）EBV末端重复序列提示病毒复制，类似于在其他免疫受损个体中发生的EBV淋巴瘤中报道的情况。早期识别这一临床问题可能有助于有益地使用抗病毒药物。
