Targeting lymphatic function as a novel therapeutic intervention for rheumatoid arthritis.
Targeting lymphatic function as a novel therapeutic intervention for rheumatoid arthritis.
复制标题
将淋巴功能作为类风湿关节炎的新型治疗干预措施。
DOI：
10.1038/nrrheum.2017.205
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Schwarz EM
中科院分区：
文献类型：
--
作者：
Bouta EM;Bell RD;Rahimi H;Xing L;Wood RW;Bingham CO 3rd;Ritchlin CT;Schwarz EM
尽管生物和常规DMARDS的使用极大地改善了类风湿性关节炎(RA)患者的临床结果，但在随机试验中，约40%的患者没有达到主要临床结果，只有一小部分患者获得了持久缓解。在过去的十年里，对小鼠模型的研究表明，淋巴系统在炎性侵蚀性关节炎的发病机制和治疗中发挥着关键作用，可能是通过从炎症的滑膜中移除分解代谢因子、细胞因子和炎性细胞。小鼠的研究表明，在炎性侵蚀性关节炎开始时，淋巴引流增加，但随着炎症进展到更慢性的阶段，淋巴清除率下降，引流淋巴结内观察到结构和细胞的变化。具体地说，持续性炎症对淋巴管的慢性损害会导致淋巴管收缩丧失，随后会导致淋巴结崩溃，淋巴引流减少，最终导致严重的滑膜炎和关节侵蚀。值得注意的是，RA患者的临床试点研究报告了治疗后淋巴结的变化，因此淋巴血管和淋巴结的引流可能代表着关节炎活动和治疗反应的潜在生物标记物。最重要的是，以淋巴管为靶点是类风湿关节炎治疗干预的一种创新策略。
Although clinical outcomes for patients with rheumatoid arthritis (RA) have greatly improved with the use of biologic and conventional DMARDs, approximately 40% of patients do not achieve primary clinical outcomes in randomized trials, and only a small proportion achieve lasting remission. Over the past decade, studies in murine models point to the critical role of the lymphatic system in the pathogenesis and therapy of inflammatory-erosive arthritis, presumably by the removal of catabolic factors, cytokines and inflammatory cells from the inflamed synovium. Murine studies demonstrate that lymphatic drainage increases at the onset of inflammatory-erosive arthritis but, as inflammation progresses to a more chronic phase, lymphatic clearance declines and both structural and cellular changes are observed in the draining lymph node. Specifically, chronic damage to the lymphatic vessel from persistent inflammation results in loss of lymphatic vessel contraction followed by lymph node collapse, reduced lymphatic drainage, and ultimately severe synovitis and joint erosion. Notably, clinical pilot studies in patients with RA report lymph node changes following treatment, and thus draining lymphatic vessels and nodes could represent a potential biomarker of arthritis activity and response to therapy. Most importantly, targeting lymphatics represents an innovative strategy for therapeutic intervention for RA.
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影响因子：
6.2
作者：
Bouta, Echoe M.;Banik, Peony D.;Schwarz, Edward M.
通讯作者：
Schwarz, Edward M.
影响因子：
3.1
作者：
Breslin, Jerome W.
通讯作者：
Breslin, Jerome W.
影响因子：
3.7
作者：
Bouta EM;Ju Y;Rahimi H;de Mesy-Bentley KL;Wood RW;Xing L;Schwarz EM
通讯作者：
Schwarz EM
影响因子：
3.7
作者：
Blum KS;Karaman S;Proulx ST;Ochsenbein AM;Luciani P;Leroux JC;Wolfrum C;Detmar M
通讯作者：
Detmar M
影响因子：
13.3
作者：
Bouta, Echoe M.;Kuzin, Igor;Schwarz, Edward M.
通讯作者：
Schwarz, Edward M.