Ma Liang, Liu Bin, Jiang Zhenyu, Jiang Yanfang
Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, Changchun, 130032, China,
Clin Rheumatol. 2014 Feb;33(2):187-95. doi: 10.1007/s10067-013-2359-3. Epub 2013 Aug 15.
This study is aimed at determining the numbers of circulating Treg and Breg cells in patients with new-onset rheumatoid arthritis and during subsequent drug therapies. Patients were treated orally with 10 mg methotrexate weekly, and 20 mg leflunomide and 60 mg common threewingnut root daily (Lei Gong Teng) for 12 weeks, but received no steroid therapy. Basal measurements were performed of serum C-reactive protein, anticyclic citrullinated peptide antibody, and erythrocyte sedimentation rate, and the numbers of cluster of differentiation CD4(+)CD25(+)Foxp3(+) T cells, interleukin 10 (IL10)-expressing on CD5(+)CD1d(+) and TIM1(+) B cells. Compared with the healthy controls, patients exhibited significantly less numbers of circulating CD19(+)TIM1(+)IL10(+), CD19(+)CD5(+)CD1d(+)IL10(+) B cells and CD4(+)CD25(+)Foxp3(+) T cells (P < 0.001, all). Drug therapy modulated the balance of different subsets of Breg and Treg cells. The numbers of CD19(+)TIM1(+)IL10(+) and CD19(+)CD5(+)CD1d(+)IL10(+) B cells correlated positively with the numbers of CD4(+)CD25(+)Foxp3(+) T cells in these patients (r = 0.707, P = 0.001; r = 0.481, P = 0.007, respectively). The values of DAS28 were negatively correlated with the numbers of CD19(+)TIM1(+)IL10(+) and CD19(+)CD5(+)CD1d(+)IL10(+) B cells, and CD4(+)CD25(+)Foxp3(+) T cells (r = -0.533, P = 0.023; r = -0.442, P = 0.016; and r = -0.444, P = 0.014, respectively). Of note, TIM1(+) B cells identified more circulating IL10(+) B cells than CD5(+)CD1d(+) B cells. Our data indicate that Breg and Treg cells have a potentially crucial role in controlling disease activity in rheumatoid arthritis patients, and TIM1(+) Breg cells may be a viable therapeutic target for these patients.
本研究旨在确定新诊断类风湿关节炎患者及后续药物治疗期间循环调节性T细胞（Treg）和调节性B细胞（Breg）的数量。患者每周口服10毫克甲氨蝶呤，每日口服20毫克来氟米特和60毫克雷公藤，持续12周，但未接受类固醇治疗。检测了血清C反应蛋白、抗环瓜氨酸肽抗体、红细胞沉降率的基础值，以及分化簇CD4(+)CD25(+)Foxp3(+) T细胞、CD5(+)CD1d(+)和TIM1(+) B细胞上表达白细胞介素10（IL10）的数量。与健康对照相比，患者循环中的CD19(+)TIM1(+)IL10(+)、CD19(+)CD5(+)CD1d(+)IL10(+) B细胞和CD4(+)CD25(+)Foxp3(+) T细胞数量显著减少（P均<0.001）。药物治疗调节了Breg和Treg细胞不同亚群之间的平衡。这些患者中，CD19(+)TIM1(+)IL10(+)和CD19(+)CD5(+)CD1d(+)IL10(+) B细胞的数量与CD4(+)CD25(+)Foxp3(+) T细胞的数量呈正相关（r分别为0.707，P = 0.001；r为0.481，P = 0.007）。疾病活动评分28（DAS28）值与CD19(+)TIM1(+)IL10(+)、CD19(+)CD5(+)CD1d(+)IL10(+) B细胞以及CD4(+)CD25(+)Foxp3(+) T细胞的数量呈负相关（r分别为-0.533，P = 0.023；r为-0.442，P = 0.016；r为-0.444，P = 0.014）。值得注意的是，TIM1(+) B细胞比CD5(+)CD1d(+) B细胞识别出更多循环中的IL10(+) B细胞。我们的数据表明，Breg和Treg细胞在控制类风湿关节炎患者的疾病活动中可能具有关键作用，且TIM1(+) Breg细胞可能是这些患者可行的治疗靶点。
