首页> 美国卫生研究院文献>Human Vaccines Immunotherapeutics >The effect of single course high dose dexamethasone on CD28/CTLA-4 balance in the treatment of patients with newly diagnosed primary immune thrombocytopenia
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The effect of single course high dose dexamethasone on CD28/CTLA-4 balance in the treatment of patients with newly diagnosed primary immune thrombocytopenia

机译:单疗程大剂量地塞米松对新诊断原发性免疫性血小板减少症患者的CD28 / CTLA-4平衡的影响

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摘要

To evaluate the effect of a single course of high dose dexamethasone (HD-DXM) on CD28 and CTLA-4 expression in patients with newly-diagnosed primary immune thrombocytopenia (ITP). Twenty-8 ITP patients (18 females and 10 males, age range 18–65 years, median age 38.5 years) enrolled in this study and 26 healthy volunteers (19 women and 7 men, age range 16–66 years, median age 37 years) served as a control group. The patients were treated with HD-DXM (40 mg/day) for 4 consecutive days. CD28 and CTLA-4 expression was assessed by flow cytometry once-monthly for 6 months. Plasma levels of the cytokines IFN-γ and IL-10 were determined by enzyme-linked immunosorbent assay. One month after treatment, a platelet response was observed in 23 (82%) of the patients. The response rates over the next 5 months were 71%, 57%, 53%, 46%, and 39%, chronologically. We observed a significant decrease in CD28 expression after the first month (34.7 ± 4.8% vs. 44.5 ± 4.4% before treatment), after which the CD28 levels gradually increased. In contrast, CTLA-4 expression increased after the first month (3.2 ± 0.5% vs. 0.8 ± 0.4 before treatment), after which the CTLA-4 levels gradually decreased. Similar dynamic changes were seen in the levels of IFN-γ and IL-10. The dynamic changes of CD28 and CTLA-4 were consistent with those of IFN-γ and IL-10 and with the effectiveness of HD-DXM in the treatment of ITP. Our results suggest that a disturbed CD28/CTLA-4 balance may contribute to the immunopathogenesis of ITP.
机译:在新诊断的原发性免疫性血小板减少症(ITP)患者中评估单疗程高剂量地塞米松(HD-DXM)对CD28和CTLA-4表达的影响。这项研究共招募了20到8名ITP患者(18名女性和10名男性,年龄范围18-65岁,中位年龄38.5岁)和26名健康志愿者(19名妇女和7名男性,年龄范围16-66岁,中位年龄37岁) )作为对照组。患者连续4天接受HD-DXM(40 mg /天)治疗。通过流式细胞术每月评估CD28和CTLA-4的表达,持续6个月。通过酶联免疫吸附测定法测定血浆细胞因子IFN-γ和IL-10的水平。治疗一个月后,在23名患者(82%)中观察到血小板反应。未来5个月的回应率按时间顺序分别为71%,57%,53%,46%和39%。我们观察到第一个月后CD28表达显着下降(治疗前为34.7±4.8%,而治疗前为44.5±4.4%),此后CD28水平逐渐升高。相比之下,第一个月后CTLA-4表达增加(治疗前为3.2±0.5%,而治疗前为0.8±0.4),之后CTLA-4水平逐渐下降。在IFN-γ和IL-10水平上也观察到类似的动态变化。 CD28和CTLA-4的动态变化与IFN-γ和IL-10的动态变化以及HD-DXM在ITP治疗中的有效性一致。我们的结果表明,CD28 / CTLA-4平衡紊乱可能与ITP的免疫发病机制有关。

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