Experimental study of the therapeutic effect of synthetic peptide for Sjogren's syndrome

人类原发性干燥综合征是一种病因不明的自身免疫性疾病，其特征在于外分泌器官如唾液腺和泪腺中的弥漫性淋巴浸润，但还没有合适的人类疾病动物模型。人们一直认为，免疫，遗传和环境因素的组合可能在唾液腺和泪腺的自身免疫性病变的发展中发挥关键作用，但对原发性干燥综合征的发病机制知之甚少。我们建立了一个原发性干燥综合征的动物模型，在NFS/sld突变小鼠携带一个常染色体隐性基因与舌下分化停滞。在出生后3天切除胸腺的这一品系小鼠中，唾液腺和泪腺自发地发生严重的自身免疫性病变。这种动物模型对于研究和阐明原发性干燥综合征中自身免疫性疾病的发病机制至关重要。最近，我们从NFS/sld动物模型的唾液腺组织中纯化了120 KDa器官特异性自身抗原。这种纯化的抗原诱导增殖性T细胞应答，以及细胞因子产生，包括IL-2和干扰素-γ。静脉注射合成肽预防小鼠器官特异性自身免疫性病变。我们推测抗120 KDa免疫应答在原发性干燥综合征的发生发展中起关键作用。

Primary Sjogren's syndrome in humans is an autoimmune disease of unknown etiology that is characterized by diffuse lymphoid infiltrates in the exocrine organs, such as the salivary and lacrimal glands, but there has not been an appropriate animal model of the human disease. It has been assumed that a combination of immunologic, genetic, and environmental factors may play a key role in development of autoimmune lesions in the salivary and lacrimal glands, but little is known about the disease pathogenesis of primary Sjogren's syndrome. We have established an animal model for primary Sjogren's syndrome in NFS/sld mutant mice bearing an autosomal recessive gene with sublingual differentiation arrest. Severe autoimmune lesions in the salivary and lacrimal glands developed spontaneously in this strain of mice thymectomized 3 day after birth. Such an animal model is essential to study and elucidate the pathogenesis of autoimmune disorders in primary Sjogren's syndrome. More recently, we purified 120KDa organ-specific autoantigen from salivary gland tissues of an NFS/sld animal model. This purified antigen induced proliferative T cell responses, as well as cytokine production including IL-2, and interferon-gamma. Intravenous injection with synthetic peptide prevented the organ-specific autoimmune lesions in mice. We can speculate that the anti-120 KDa immune response play a critical role in the development of primary Sjogren's syndrome.