基于Tfh/Tfr平衡解析井下作业工人类风湿关节炎的机制研究

Rheumatoid arthritis (RA) is a kind of autoimmune disease that T cell-mediated, B cell hypofunction and involving the soft tissues around the joints. Underground workers regularly expose to kinds of occupational hazards, such as "wind, cold, wet" and the incidence of RA is higher. However, how occupational and environmental factors influence human immune status is far from clear. This subject intends to use Tfh/Tfr balance as the main point, to analysis the immune process and pathological features of underground workers risking RA by comparing to general RA, in order to probe the possibility that whether it can be a warning marker to characterize disease prognosis. On the basis, we try to use Meridian buried line therapy and TCM treatment to treat RA patients, to investigate an effective way to treat RA induced by extreme environmental factors. Finally, we may explore preliminary molecular mechanisms during rebalance Tfh/ Tfr ratio and reversal of joint synovium autoimmune process of underground workers with RA.

类风湿关节炎(RA)是一类主要由T细胞介导、B细胞异常亢进累及关节及周围软组织的自身免疫性疾病。井下作业工人长期暴露于“风、寒、湿”等多种职业危害因素中，RA发病率较高，但职业环境因素如何影响机体的自身免疫状态还远未阐明。本课题拟以Tfh/Tfr平衡为主要关注点，通过与常规RA的对比，分析井下作业工人罹患RA的免疫病理过程及其特点，探究其成为预警和疾病预后新指标的可能；在此基础上，应用沿经络埋线疗法对比中医治疗井下工人RA和普通人群RA的疗效反应，探索治疗极端环境诱发RA有效的治疗手段；进而探索靶向Tfh/Tfr平衡抑制和逆转井下作业工人RA患者关节滑膜自身免疫过程的初步分子调控机制。

本项目以井下作业的职业性尘肺病患者为研究对象，系统分析了该类型职业病患者外周血的典型淋巴细胞亚群的变化，发现Tfr/Tfh平衡改变可能是环境和职业因素对该人群免疫平衡影响的典型表现。同时，根据传统中医经络腧穴理论，选择足太阳膀胱经等经络段作为施治部位，采用经络埋线疗法并辅以玻璃酸钠注射来治疗RA，取得了显著的疗效。课题组通过系统的分析患者治疗前后典型T淋巴细胞亚群的变化，初步提出了本疗法纠正RA患者体内免疫平衡失衡的可能的细胞学机制，即通过再平衡Tfr和Tfhem细胞之间的比例实现对过度活化的自身免疫免疫应答的纠正，为深入研究RA发病和转归的规律，进一步扩大本疗法的临床应用范围提供了新的视角。

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