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

人类原发干燥综合征是一种自身免疫性疾病，以涎腺和泪腺弥漫性淋巴样细胞浸润为特征，出现口干、眼干的症状，提示分泌不足。该病的表现范围很广，从器官局限性的外分泌腺功能障碍到全身并发症，如肝、肾和肺受累。此外，很大比例的SS患者可能会发展为恶性淋巴增生性疾病，如B细胞淋巴瘤和巨球蛋白血症。虽然人们认为免疫、遗传和环境因素可能在涎腺和泪腺自身免疫性病变的发生发展中起关键作用，但对人类原发SS的发病机制知之甚少。人们对包括SS在内的人类自身免疫性疾病的不同免疫学方面的研究非常感兴趣。唾液腺的功能低下是由于淋巴细胞的渗透，通常认为自身反应性T细胞识别未知的自身抗原并在SS的发病机制中发挥核心作用。原发SS的特征还包括全身产生针对核糖核蛋白(RNP)颗粒SS-A/Ro和SS-B/La的自身抗体，但SS-A和SS-B免疫原性的特异性尚不清楚。尽管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(S)，但我们最近已确定120KD的α-fodrin是在动物模型和SS患者中SS发生发展过程中的一个重要的唾液腺自身抗原。

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.