不同结局结节病血清学标记物动态变化及免疫机制研究

结节病是一种全身系统性肉芽肿性疾病，可累及多个器官，主要累及肺部。其病因不明，临床表现多样，临床结局迥然不同，部分患者可自愈或对激素治疗反应良好，而部分患者治疗过程中易复发甚至进展为肺纤维化。大量研究表明结节病的发生伴随着外周血免疫微环境的变化。那么不同结局的结节病患者其外周血免疫微环境有何不同？是否存在某些特定的蛋白或细胞因子与免疫细胞相互作用导致免疫微环境变化不同？本课题组前期研究发现结节病患者外周血中存在3种可能的特异性蛋白标记物，且发现外周血Th17/Treg细胞失衡在结节病活动与进展过程中发挥重要的免疫调控作用。本研究从血清学角度出发，筛查验证不同结局的结节病患者血清标记物的动态变化，分析外周血固有免疫及适应性免疫应答变化特征，并探讨生物标记物与结节病全身免疫微环境变化之间及其与预后的关系，阐释结节病自愈、复发、进展等不同转归发生的免疫机制，为疾病预测及病程监测提供新思路。

Sarcoidosis is a multisystem granulomatous inflammatory disorder that most commonly affects the lungs and intrathoracic lymph nodes. The etiology is unclear and clinical manifestations are protean. Prognosis may be very different, some patients resolve themselves without treatment, some patients tending to recrudesce during glucocorticoid therapy, while some patients even developing pulmonary fibrosis. Plenty of studied point that immunity imbalance play key roles in the pathogenesis of sarcoidosis. What makes the immuno-microenvironment so different in different outcome of sarcoidosis. Is there any protein acting on some immune cells? In the previous study we found that there were three kinds of sarcoidosis specific protein biomarkers in peripheral blood. We also found that Th17/Treg cells may function in the activity and progresses of sarcoidosis. In the current study we will focus on serology to screen the specific protein biomarkers in peripheral blood which associated with prognosis, to reveal the connection between thee markers and the characteristic changes of the innate and adaptive immunity function, and to demonstrate the mechanism of self-resolving, relapse and worsening into pulmonary fibrosis in the process of sarcoidosis. This study will provide new insights for predict the trend and monitoring of sarcoidosis.