Eculizumab treatment modifies the immune profile of PNH patients
Eculizumab treatment modifies the immune profile of PNH patients
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DOI：
10.1016/j.imbio.2011.11.009
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发表时间：
2012-07-01
期刊：
影响因子：
2.8
通讯作者：
Terrazzano, Giuseppe
中科院分区：
文献类型：
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作者：
Alfinito, Fiorella;Ruggiero, Giuseppina;Terrazzano, Giuseppe
阵发性睡眠性血红蛋白尿症(PNH)是由于携带PIG-A基因体细胞突变的干祖细胞病理性扩张所致，PIG-A基因参与糖基磷脂酰肌醇(GPI)锚的生物合成。大量数据表明，免疫调节机制在GPI缺陷克隆的选择/扩增中发挥了作用。PNH中的溶血性贫血依赖于补体对GPI缺陷红细胞的作用。Eculizumab是一种抗C5的单抗，在控制溶血和血栓形成、减轻疲劳和改善患者的生活质量方面非常有效。然而，这种治疗提出了新的挑战，需要正确面对。在这里，我们报告了在Eculizumab治疗前PNH患者B自然杀伤细胞(NK)和调节性T细胞(Treg)的减少，不变NKT细胞(NKTi)细胞因子谱的改变以及C-X-C趋化因子受体4(CXCR4)受体的增加。治疗对其中一些变化有显著影响：Eculizumab治疗后，B淋巴细胞数量、NKTi分泌的细胞因子和CD8T细胞上CXCR4的表达与健康献血者相似。未观察到对NK和Treg的影响。GPI缺陷区的波幅保持不变。(C)爱思唯尔股份有限公司。版权所有。
Paroxysmal Nocturnal Haemoglobinuria (PNH) is due to pathological expansion of a stem progenitor bearing a somatic mutation of PIG-A gene involved in the biosynthesis of the glycosyl-phosphatidyl-inositol (GPI) anchor. Numerous data suggest a role for immune-mediated mechanisms in the selection/expansion of GPI-defective clone. Haemolytic anaemia in PNH is dependent on the effect of complement against GPI-defective red cells. Eculizumab, an anti-C5 monoclonal antibody, is dramatically effective in controlling haemolysis and thrombosis, in reducing fatigue and in improving quality of life of patients. However, this therapy presents new challenges that need to be properly faced.Here, we report the decrease in B. Natural Killer (NK) and regulatory T cells (Treg), an altered cytokine profile of invariant-NKT cells (NKTi) and the increasing of C-X-C chemokine receptor type 4 (CXCR4) receptor in PNH patients before the Eculizumab therapy. Treatment significantly affects some of these alterations: after Eculizumab, the number of B lymphocytes, the cytokine secretion of NKTi and CXCR4 expression on CD8 T cells became similar to healthy donors. No effects were observed on NK and Treg. The amplitude of the GPI-defective compartment remained unchanged. (C) Elsevier GmbH. All rights reserved.