A study of molecular pathology in experimental Sjogren's syndrome in mice

原发性干燥综合征（Primary shjogren syndrome， SS）是一种以弥漫性淋巴样细胞浸润于唾液腺和泪腺为特征的自身免疫性疾病，其症状表现为口干和眼干，提示分泌不足。该病的表现范围很广，从器官局限性外分泌腺功能障碍到全身并发症，如肝、肾和肺受累。此外，相当比例的SS患者可发展为恶性淋巴细胞增生性疾病，如B细胞淋巴瘤和巨球蛋白血症。虽然人们一直认为免疫、遗传和环境因素的结合可能在唾液和泪腺自身免疫性病变的发展中起关键作用，但对人类原发性SS的发病机制知之甚少。唾液腺功能减退是由淋巴细胞浸润引起的，一般认为自身反应性T细胞识别未知的自身抗原，并在SS的发病机制中起核心作用。原发性SS还以系统产生针对核糖核蛋白（RNP）颗粒SS-A/Ro和SS- b / La的自身抗体为特征。但SS-A和SS-B的免疫原性特异性尚不清楚。虽然目前尚不清楚是否存在与人类原发性SS相关的关键器官特异性自身抗原，但我们最近发现120KD α -fodrin是动物模型和SS患者中SS发展的重要唾液腺自身抗原。

Primary Sjogren syndrome (SS) in humans is an autoimmune disease characterized by diffuse lymphoid cell infiltrates in the salivary and lacrimal glands, resulting in symptoms of dry mouth and dry eye clue to insufficient secretion. The spectrum of presentation of the disease is broad, ranging from the organ-localized dysfunction of exocrine gland to systemic complications such as liver, kidney and lung involvement. Moreover, a significant proportion of the SS patients may develop malignant lymphoproloferative disorders such as B cell lymphoma and macroglobulinemia. Although it has been assumed that a combination of immunologic, genetic, and environmental factors may play a key role on the development of autoimmune lesion in the salivary and lacrimal gland, little is known about the disease pathogenesis of primary SS in humans. A great interest is to investigate different immunological aspects of human autoimmune diseases including SS.The hypofunction of the salivary glands is due to lymphocytic infiltration, in which it is generally assumed that autoreactive T cells recognize unknown self-antigen and play a central role in the pathogenesis of SS.Primary SS is also characterized by systemic production of autoantibodies to ribonucleoprotein (RNP) particles SS-A/Ro and SS-B/ La, but the specificity for the immunogenicity of SS-A and SS-B remains unclear. Although it has been unclear whether or not there are critical organ-specific autoantigen(s) relevant to human primary SS, we have recently identified the 120KD alpha-fodrin as an important salivary gland autoantigen on the development of SS in both animal model and SS patients.