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多发性硬化症患者的单核细胞和淋巴细胞激活与调节。治疗效果。

Monocyte and Lymphocyte Activation and Regulation in Multiple Sclerosis Patients. Therapy Effects.

机构信息

Servicio de Neurología, Hospitales Universitarios Virgen del Rocío, Seville, Spain.

Servicio de Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Avda Ana de Viya s/n, 11009, Cádiz, Spain.

出版信息

J Neuroimmune Pharmacol. 2019 Sep;14(3):413-422. doi: 10.1007/s11481-018-09832-z. Epub 2019 Jan 16.

Abstract

Analysis of gut barrier status, monocyte and lymphocyte activation and T regulatory (Treg) cells at diagnosis before and after therapy, in patients with multiple sclerosis (MS). Analysis of differential effects of interferon beta (IFN-β), glatiramer acetate (GA) and natalizumab. Thirty-five patients with untreated MS were included. Gut barrier status (serum concentrations of intestinal fatty acid binding protein), monocyte (serum levels of soluble CD14, soluble CD163 and interleukin 6) and T lymphocyte activation (CD4 + DR+ and CD8 + DR+) and Treg (CD4 + CD25highFoxP3+) cells were analyzed. Patients with clinical isolated syndrome and relapsing-remitting forms were treated with IFN-β or GA, and immune characteristics were reevaluated following up after 6 months. A sample of 56 stable RR MS patients, in treatment with IFN-β, GA or natalizumab, and 50 healthy individuals were included as controls. Gut barrier status was similar in MS patients and healthy controls. Untreated patients with relapsing-remitting and primary progressive patterns of MS showed increased serum levels of soluble CD14. At baseline, significant increases in activated T lymphocytes and Treg were detected in patients. A significant decrease of CD4 + DR+, CD8 + DR+, and Treg percentages after 6 months of therapy was observed. In previously treated patients, IFN-β, GA, or natalizumab therapies were associated with a comparable cell proportion of activated lymphocytes and Treg. MS patients have a baseline state characterized by monocyte and lymphocyte activation, not related with gut barrier lesion. An increase in Treg number, correlated with activated T CD8+ lymphocytes, was detected. Treatment with IFN-β, GA or natalizumab was associated with a comparable decrease in activated lymphocytes and Treg. Graphical Abstract ᅟ.

摘要

多发性硬化症(MS)患者治疗前后诊断时肠道屏障状态、单核细胞和淋巴细胞激活以及 T 调节(Treg)细胞的分析。分析干扰素-β(IFN-β)、聚乙二醇干扰素β-1a(GA)和那他珠单抗的差异作用。纳入 35 例未经治疗的 MS 患者。分析肠道屏障状态(血清肠脂肪酸结合蛋白浓度)、单核细胞(血清可溶性 CD14、可溶性 CD163 和白细胞介素 6 水平)和 T 淋巴细胞激活(CD4+DR+和 CD8+DR+)以及 Treg(CD4+CD25highFoxP3+)细胞。临床孤立综合征和复发缓解型患者接受 IFN-β 或 GA 治疗,治疗后 6 个月进行免疫特征再评估。纳入 56 例稳定 RRMS 患者(接受 IFN-β、GA 或那他珠单抗治疗)和 50 例健康对照者作为对照。MS 患者和健康对照者的肠道屏障状态相似。复发缓解型和原发性进行性 MS 患者的可溶性 CD14 血清水平升高。基线时,患者激活的 T 淋巴细胞和 Treg 显著增加。治疗 6 个月后,CD4+DR+、CD8+DR+和 Treg 百分比显著降低。先前接受治疗的患者中,IFN-β、GA 或那他珠单抗治疗与激活淋巴细胞和 Treg 的可比细胞比例相关。MS 患者存在以单核细胞和淋巴细胞激活为特征的基线状态,与肠道屏障损伤无关。检测到 CD8+T 细胞激活相关的 Treg 数量增加。IFN-β、GA 或那他珠单抗治疗与激活淋巴细胞和 Treg 的可比减少相关。图表摘要 ᅟ。

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