微小 RNA 表达显示感染后莱姆关节炎患者关节中的炎症失调和类似肿瘤的增殖反应。
MicroRNA Expression Shows Inflammatory Dysregulation and Tumor-Like Proliferative Responses in Joints of Patients With Postinfectious Lyme Arthritis.
机构信息
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Yale University School of Medicine, New Haven, Connecticut.
出版信息
Arthritis Rheumatol. 2017 May;69(5):1100-1110. doi: 10.1002/art.40039.
OBJECTIVE
Lyme arthritis (LA) is caused by infection with Borrelia burgdorferi and usually resolves following spirochetal killing with antibiotics. However, in some patients, arthritis persists after antibiotic therapy. To provide insights into underlying pathogenic processes associated with antibiotic-refractory LA (postinfectious LA), we analyzed differences in microRNA (miRNA) expression between LA patients with active infection and those with postinfectious LA.
METHODS
MicroRNA expression was assayed in synovial fluid (SF) from LA patients before and after oral and intravenous antibiotic therapy, and in synovial tissue obtained months after antibiotic therapy from patients with postinfectious LA. SF and tissue from patients with other forms of arthritis, such as rheumatoid arthritis (RA) and osteoarthritis, were used for comparison.
RESULTS
SF from LA patients during active infection had marked elevations of white blood cells, particularly polymorphonuclear leukocytes, accompanied by elevated levels of microRNA-223 (miR-223). In contrast, SF from postantibiotic LA patients contained greater percentages of lymphocytes and mononuclear cells. SF from postantibiotic LA patients also exhibited marked inflammatory (miR-146a, miR-155), wound repair (miR-142), and proliferative (miR-17-92) miRNA signatures, and higher levels of these miRNAs correlated with longer arthritis duration. Levels of miR-146a, miR-155, miR-142, miR-223, and miR-17-92 were also elevated in synovial tissue in late postinfectious LA, and levels of let-7a were reduced, similar to RA.
CONCLUSION
During active infection, miRNA expression in SF reflected an immune response associated with bacterial killing, while in postinfectious LA, miRNA expression in SF and synovial tissue reflected chronic inflammation, synovial proliferation, and breakdown of wound repair processes, showing that the nature of the arthritis was altered after spirochetal killing.
目的
莱姆关节炎（LA）是由伯氏疏螺旋体感染引起的，通常在螺旋体被抗生素杀死后关节炎会痊愈。然而，在一些患者中，关节炎在抗生素治疗后仍持续存在。为了深入了解与抗生素难治性 LA（感染后 LA）相关的潜在发病机制，我们分析了 LA 患者在感染活动期和感染后 LA 患者之间滑膜液（SF）中 microRNA（miRNA）表达的差异。
方法
在口服和静脉抗生素治疗前后，检测 LA 患者 SF 中 miRNA 的表达，并在感染后 LA 患者抗生素治疗数月后获得滑膜组织。将 SF 和组织与其他形式的关节炎患者（如类风湿关节炎（RA）和骨关节炎）进行比较。
结果
LA 患者在感染活动期 SF 中白细胞，尤其是多形核白细胞显著升高，同时伴有 microRNA-223（miR-223）水平升高。相比之下，LA 患者在抗生素治疗后的 SF 中含有更多比例的淋巴细胞和单核细胞。SF 中的 postantibiotic LA 患者还表现出明显的炎症（miR-146a、miR-155）、伤口修复（miR-142）和增殖（miR-17-92）miRNA 特征，并且这些 miRNA 的水平与关节炎持续时间更长相关。miR-146a、miR-155、miR-142、miR-223 和 miR-17-92 在晚期 postinfectious LA 的滑膜组织中也升高，let-7a 水平降低，类似于 RA。
结论
在感染活动期，SF 中的 miRNA 表达反映了与细菌杀伤相关的免疫反应，而在感染后 LA 中，SF 和滑膜组织中的 miRNA 表达反映了慢性炎症、滑膜增殖和伤口修复过程的破坏，表明关节炎的性质在螺旋体被杀死后发生了改变。
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