B细胞激活因子-BAFF在干燥综合征发病机制中的作用研究

Sjogren's syndrome(SS) is a systemic autoimmune disease.It has been proposed that increased levels of B cell activationg factor(BAFF) breach B cell tolerance in SS by enhancing survival of self-reactive B cells, thus leading to a lot of inflamatory lesions in SS. By our previous study, we discovered increasing levels of BAFF in serum and salivary glands of SS patients, which might related with antibodies production and germinal center formation. BAFF Transgenic mice also prodused SS related autoantibodies in serum, and were manifested as lymphocyte infiltration in its salivary gland. We also composed BAFF-polypeptied-Fc fusion protein to antagonise the receptor of BAFF to study the thereaputic effects of BAFF antagonists in SS. However, it is unclear if BAFF is sufficient to produce these abnormalities in SS, so it is immportant to explore the pathogenesis of BAFF in SS. This project will reveal them through different aspects of molecule, cell, animals and patients. The discoveries will shed light on the designs of new strategies to treat SS.

干燥综合征（SS）是一种T细胞介导、B细胞亢进导致的多系统受累的自身免疫性疾病，其中BAFF的异常表达可导致B细胞成熟分化、分泌大量免疫球蛋白并产生多种致病性自身抗体，使机体出现炎症反应和破坏。我们前期研究发现SS患者血清和唇腺组织中可溶性BAFF和膜BAFF表达均明显升高，且与唇腺异位生发中心形成和血清免疫球蛋白水平相关；BAFF转基因鼠也随年龄进展逐渐出现血清高滴度SS相关自身抗体及标志性病理损伤-颌下腺灶性淋巴细胞浸润；课题组同时合作构建质粒并纯化了BAFF受体及受体多肽-Fc融合蛋白抗体作为BAFF拮抗剂预予实验性靶向治疗，以期了解其调控疗效和机制。本课题将围绕干燥综合征研究BAFF影响疾病的分子机制，并针对BAFF进行拮抗治疗，从细胞、患者、分子和动物四个层面深入探讨BAFF在SS发病过程中的免疫调控机制，对阐明BAFF在SS发病中的作用及其靶向治疗有重要意义。

干燥综合征（SS）是一种T细胞介导、B细胞亢进导致的多系统受累的自身免疫性疾病，其中B细胞活化因子-BAFF的异常表达可导致B细胞成熟、分化、分泌大量免疫球蛋白并产生多种致病性自身抗体，使机体出现炎症反应和破坏。本课题研究发现SS患者血清和唇腺组织中可溶性BAFF和膜BAFF表达均明显升高，且与患者唇腺异位生发中心形成和体内免疫球蛋白水平相关；BAFF 转基因小鼠也随年龄进展逐渐出现血清高滴度SS相关自身抗体及颌下腺灶性淋巴细胞浸润；课题组同时合作构建质粒并纯化了BAFF受体和受体多肽-Fc融合蛋白作为BAFF拮抗剂预予实验性靶向治疗，该研究在顺利进行中。本课题初步明确了BAFF如何参与干燥综合征的发病及其对疾病的影响，对阐明BAFF在SS发病中的作用及其靶向治疗具有重要意义。