Treg Cell Numbers and Function in Patients With Antibiotic-Refractory or Antibiotic-Responsive Lyme Arthritis
Treg Cell Numbers and Function in Patients With Antibiotic-Refractory or Antibiotic-Responsive Lyme Arthritis
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DOI：
10.1002/art.27468
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发表时间：
2010-07-01
影响因子：
--
通讯作者：
Steere, Allen C.
中科院分区：
文献类型：
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作者：
Shen, Shiqian;Shin, Junghee J.;Steere, Allen C.
Objective.在难治性莱姆病关节炎的鼠模型中，Treg细胞的数量显著减少。本研究旨在检测难治性莱姆病关节炎患者Treg细胞的数量和功能。对12例难治性关节炎和6例反应性关节炎患者外周血和关节液中的CD 4 + T细胞亚群进行了计数。使用疏螺旋体特异性和非特异性Treg细胞增殖试验检测Treg细胞功能。在两个患者组中，SF中的干扰素-γ阳性Th 1细胞丰富且富集（类似于50%的CD 4 + T细胞）。在难治性关节炎患者中，SF中FoxP 3阳性Treg细胞的中位百分比显著高于PB（12% vs 6%; P = 0.03）或来自关节炎反应性关节炎患者的SF（12% vs 5%; P = 0.04）。此外，在难治性关节炎组中，SF中Treg细胞百分比较高与关节炎消退时间较短相关（r =-0.74，P = 0.006）。相比之下，Treg细胞较少的患者对疾病缓解抗风湿药物的反应不佳，抗生素治疗后关节炎的持续时间较长，并且他们通常需要滑膜切除术来解决关节炎。在每组中，SF中的Treg细胞抑制了伯氏疏螺旋体特异性增殖反应，在2例难治性关节炎患者中，Treg细胞在非特异性抑制试验中起作用。Treg细胞在难治性关节炎患者中是有功能的，并且在一些患者中，SF中更多数量的这些细胞似乎参与关节炎的消退。然而，在小鼠模型中，患有难治性关节炎和Treg细胞数量较低的患者似乎无法实现滑膜炎症的消退。
Objective. In a murine model of antibiotic-refractory Lyme arthritis, the numbers of Treg cells are dramatically reduced. The aim of this study was to examine Treg cell numbers and function in patients with antibiotic-refractory Lyme arthritis.Methods. CD4+ T cell subsets were enumerated in the peripheral blood (PB) and synovial fluid (SF) of 12 patients with antibiotic-refractory arthritis and 6 patients with antibiotic-responsive arthritis. Treg cell function was examined using Borrelia-specific and nonspecific Treg cell proliferation assays.Results. In both patient groups, interferon-gamma positive Th1 cells in SF were abundant and enriched (similar to 50% of CD4+ T cells). In patients with antibiotic-refractory arthritis, the median percentages of FoxP3-positive Treg cells were significantly higher in SF than in PB (12% versus 6%; P = 0.03) or in SF from patients with antibiotic-responsive arthritis (12% versus 5%; P = 0.04). Moreover, in the antibiotic-refractory group, a higher percentage of Treg cells in SF correlated with a shorter duration until resolution of arthritis (r = -0.74, P = 0.006). In contrast, patients with fewer Treg cells had suboptimal responses to disease-modifying antirheumatic drugs and a longer duration of arthritis after antibiotic treatment, and they often required synovectomies for arthritis resolution. In each group, Treg cells in SF dampened Borrelia burgdorferi-specific proliferative responses, and in 2 patients with antibiotic-refractory arthritis, Treg cells were functional in nonspecific suppression assays.Conclusion. Treg cells were functional in patients with antibiotic-refractory arthritis, and in some patients, higher numbers of these cells in SF appeared to participate in arthritis resolution. However, as in the murine model, patients with antibiotic-refractory arthritis and lower numbers of Treg cells seemed unable to achieve resolution of synovial inflammation.