Administration of Intravenous Iron Formulations Induces Complement Activation in-vivo
Administration of Intravenous Iron Formulations Induces Complement Activation in-vivo
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DOI：
10.3389/fimmu.2019.01885
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发表时间：
2019-08-21
影响因子：
7.3
通讯作者：
Seelen, Marc A.
中科院分区：
文献类型：
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作者：
Faria, Bernardo;da Costa, Mariana Gaya;Seelen, Marc A.
背景：静脉铁剂广泛用于治疗慢性肾脏病患者的贫血。以前，铁制剂显示出在体外诱导免疫活化。目前的研究旨在探讨IV铁在体内补体激活的影响，以及这是否随后诱导炎症和/或氧化stress.Methods：两个不同的患者组包括：51非透析和32透析患者。非透析组根据医生的选择接受蔗糖铁或羧基麦芽糖铁。在IV铁输注完成之前和之后1小时收集血浆样品。透析组仅接受蔗糖铁。在两次连续血液透析开始和结束时采集血浆样本，一次使用IV铁，一次不使用IV铁。结果：在非透析组中，静脉铁剂治疗后sC 5 b-9水平显著升高32%，而MBL、C1 q、备解素、D因子、sC 5 b-9、MPO、PTX 3水平显著降低。亚组分析表明，蔗糖铁诱导补体激活，而羧基麦芽糖铁没有。在透析组中，sC 5 b-9水平在IV铁剂透析期间显著增加了46%，而因子D水平显著下降。此外，IV铁导致的因子D的相对降低与IV铁导致的sC 5 b-9的相对升高显著相关。MPO水平在静脉铁剂透析期间显著升高，但在不含铁剂的透析期间则没有显著升高。此外，MPO和sC 5 b-9的相对增加与IV铁显著相关。PTX 3水平不受IV铁。结论：铁蔗糖，但不是铁羧基麦芽糖，结果补体激活可能通过凝集素和替代途径部分介导氧化应激，但不是炎症。
Background: Intravenous (IV) iron is widely used to treat anemia in chronic kidney disease patients. Previously, iron formulations were shown to induce immune activation in-vitro. The current study aimed to investigate the effect of IV iron on complement activation in-vivo, and whether this subsequently induces inflammation and/or oxidative stress.Methods: Two distinct patient groups were included: 51 non-dialysis and 32 dialysis patients. The non-dialysis group received iron sucrose or ferric carboxymaltose, based on physicians' choice. Plasma samples were collected prior to and 1 h after completion of IV iron infusion. The dialysis group received iron sucrose exclusively. Plasma samples were collected at the start and end of two consecutive hemodialysis sessions, one with and one without IV iron. Finally, plasma levels of MBL, C1q, properdin, factor D, sC5b-9, MPO, PTX3 were assessed by ELISA.Results: In the non-dialysis group, sC5b-9 levels significantly increased after IV iron by 32%, while levels of factor D and MBL significantly dropped. Subgroup analysis demonstrated that iron sucrose induced complement activation whereas ferric carboxymaltose did not. In the dialysis group, levels of sC5b-9 significantly increased by 46% during the dialysis session with IV iron, while factor D levels significantly fell. Furthermore, the relative decrease in factor D by IV iron correlated significantly with the relative increase in sC5b-9 by IV iron. MPO levels rose significantly during the dialysis session with IV iron, but not in the session without iron. Moreover, the relative increase in MPO and sC5b-9 by IV iron correlated significantly. PTX3 levels were not affected by IV iron.Conclusions: Iron sucrose but not ferric carboxymaltose, results in complement activation possibly via the lectin and alternative pathway partially mediating oxidative stress but not inflammation.