难治性免疫性血小板减少症经过一、二线药物治疗均无效,或脾切除无效/术后复发。难治性患者血小板计数低,出血风险高,常规治疗手段效果有限,其机制尚不清楚。本文从T细胞的通路、异常活化及受体三方面展开,通路方面我们发现T细胞的特异...难治性免疫性血小板减少症经过一、二线药物治疗均无效,或脾切除无效/术后复发。难治性患者血小板计数低,出血风险高,常规治疗手段效果有限,其机制尚不清楚。本文从T细胞的通路、异常活化及受体三方面展开,通路方面我们发现T细胞的特异性克隆导致细胞毒性增加,并触发血小板活化和凋亡,甲基化诱导一些敏感基因的表达,导致免疫的失衡,使得基因下游的细胞因子释放异常,从而影响血小板的增殖及凋亡,MDSC (髓源性抑制细胞)会释放一些抑制性配体阻碍T细胞的增殖,挽救LKB1-AMPK信号通路分子和抑制性细胞因子的表达缺陷,增强了T细胞增殖。T细胞异常活化导致一些细胞因子的持续表达或相对消除,致使对一线治疗无反应。受体方面发现CD8+ T细胞毒性高的人群中Neu1易位程度高,抗GPIb/IX抗体似乎会导致更多的血小板凋亡,抑制其活性,血小板的唾液酸化会减少。通过这三方面来总结导致难治性ITP可能发生的机制,为诊断难治性ITP的新型标志物或为治疗靶点提供更多的信息。Refractory immune thrombocytopenia is ineffective after first- and second-line drug therapy, or splenectomy is ineffective/relapsed after surgery. Refractory patients have low platelet counts, high bleeding risk, and limited response to conventional treatments, and the mechanism is unclear. This article focuses on the pathways, abnormal activation, and receptors of T cells. In this paper, we found that the specific cloning of T cells leads to increased cytotoxicity and triggers platelet activation and apoptosis, methylation induces the expression of some sensitive genes, resulting in an imbalance of immunity, which makes the cytokine release downstream of genes abnormal, thereby affecting the proliferation and apoptosis of platelets, and MDSCs (myeloid-derived suppressor cells) will release some inhibitory ligands to hinder the proliferation of T cells and rescue LKB1-AMPK Defective expression of signaling pathway molecules and inhibitory cytokines enhances T cell proliferation. Aberrant T cell activation results in sustained expression or relative elimination of some cytokines, resulting in non-response to first-line therapy. In terms of receptors, it was found that the degree of Neu1 translocation was high in people with high CD8+ T cytotoxicity, and anti-GPIb/IX antibodies appeared to cause more platelet apoptosis, inhibit their activity, and reduce platelet sialylation. Through these three aspects, we summarize the mechanisms that may lead to the occurrence of refractory ITP, and provide more information for new markers for diagnosing refractory ITP or for therapeutic targets.展开更多
伴有镁缺陷的X连锁免疫缺陷病(X-linked immunodeficiency with magnesium defect and Epstein-Barr virus infection and neoplasia,XMEN)是一种由镁转运蛋白1(MAGT1)致病性功能缺失突变引起的罕见原发性免疫缺陷病(primary immunodefi...伴有镁缺陷的X连锁免疫缺陷病(X-linked immunodeficiency with magnesium defect and Epstein-Barr virus infection and neoplasia,XMEN)是一种由镁转运蛋白1(MAGT1)致病性功能缺失突变引起的罕见原发性免疫缺陷病(primary immunodeficiency disease,PID) [1] 。XMEN临床表现多变且多依赖于病例报告,典型特征为对EB病毒(EBV)易感性增加、病毒载量高及继发EBV相关淋巴瘤。北京清河医院收治1例XMEN综合征合并中性粒细胞减少病例,现报告如下。展开更多
目的:探讨中性粒细胞与淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)对儿童免疫性血小板减少症(immune thrombocytopenia,ITP)的诊断价值。方法:收集112例ITP儿童作为观察组,记录入院时的中性粒细胞计数、淋巴细胞计数,并计算NLR...目的:探讨中性粒细胞与淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)对儿童免疫性血小板减少症(immune thrombocytopenia,ITP)的诊断价值。方法:收集112例ITP儿童作为观察组,记录入院时的中性粒细胞计数、淋巴细胞计数,并计算NLR,以同年龄段51例正常儿童作为对照组,分析NLR对儿童ITP的诊断价值。结果:观察组的NLR(0.75±0.59)和对照组的NLR(0.76±0.36)比较无明显统计学差异(P>0.05)。结论:NLR对儿童ITP的诊断无参考意义。展开更多
文摘难治性免疫性血小板减少症经过一、二线药物治疗均无效,或脾切除无效/术后复发。难治性患者血小板计数低,出血风险高,常规治疗手段效果有限,其机制尚不清楚。本文从T细胞的通路、异常活化及受体三方面展开,通路方面我们发现T细胞的特异性克隆导致细胞毒性增加,并触发血小板活化和凋亡,甲基化诱导一些敏感基因的表达,导致免疫的失衡,使得基因下游的细胞因子释放异常,从而影响血小板的增殖及凋亡,MDSC (髓源性抑制细胞)会释放一些抑制性配体阻碍T细胞的增殖,挽救LKB1-AMPK信号通路分子和抑制性细胞因子的表达缺陷,增强了T细胞增殖。T细胞异常活化导致一些细胞因子的持续表达或相对消除,致使对一线治疗无反应。受体方面发现CD8+ T细胞毒性高的人群中Neu1易位程度高,抗GPIb/IX抗体似乎会导致更多的血小板凋亡,抑制其活性,血小板的唾液酸化会减少。通过这三方面来总结导致难治性ITP可能发生的机制,为诊断难治性ITP的新型标志物或为治疗靶点提供更多的信息。Refractory immune thrombocytopenia is ineffective after first- and second-line drug therapy, or splenectomy is ineffective/relapsed after surgery. Refractory patients have low platelet counts, high bleeding risk, and limited response to conventional treatments, and the mechanism is unclear. This article focuses on the pathways, abnormal activation, and receptors of T cells. In this paper, we found that the specific cloning of T cells leads to increased cytotoxicity and triggers platelet activation and apoptosis, methylation induces the expression of some sensitive genes, resulting in an imbalance of immunity, which makes the cytokine release downstream of genes abnormal, thereby affecting the proliferation and apoptosis of platelets, and MDSCs (myeloid-derived suppressor cells) will release some inhibitory ligands to hinder the proliferation of T cells and rescue LKB1-AMPK Defective expression of signaling pathway molecules and inhibitory cytokines enhances T cell proliferation. Aberrant T cell activation results in sustained expression or relative elimination of some cytokines, resulting in non-response to first-line therapy. In terms of receptors, it was found that the degree of Neu1 translocation was high in people with high CD8+ T cytotoxicity, and anti-GPIb/IX antibodies appeared to cause more platelet apoptosis, inhibit their activity, and reduce platelet sialylation. Through these three aspects, we summarize the mechanisms that may lead to the occurrence of refractory ITP, and provide more information for new markers for diagnosing refractory ITP or for therapeutic targets.
文摘伴有镁缺陷的X连锁免疫缺陷病(X-linked immunodeficiency with magnesium defect and Epstein-Barr virus infection and neoplasia,XMEN)是一种由镁转运蛋白1(MAGT1)致病性功能缺失突变引起的罕见原发性免疫缺陷病(primary immunodeficiency disease,PID) [1] 。XMEN临床表现多变且多依赖于病例报告,典型特征为对EB病毒(EBV)易感性增加、病毒载量高及继发EBV相关淋巴瘤。北京清河医院收治1例XMEN综合征合并中性粒细胞减少病例,现报告如下。
文摘目的:探讨中性粒细胞与淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)对儿童免疫性血小板减少症(immune thrombocytopenia,ITP)的诊断价值。方法:收集112例ITP儿童作为观察组,记录入院时的中性粒细胞计数、淋巴细胞计数,并计算NLR,以同年龄段51例正常儿童作为对照组,分析NLR对儿童ITP的诊断价值。结果:观察组的NLR(0.75±0.59)和对照组的NLR(0.76±0.36)比较无明显统计学差异(P>0.05)。结论:NLR对儿童ITP的诊断无参考意义。
