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