NK cell frequency and cytotoxicity in correlation to pregnancy outcome and response to IVIG therapy among women with recurrent pregnancy loss

NK cell frequency and cytotoxicity in correlation to pregnancy outcome and response to IVIG therapy among women with recurrent pregnancy loss
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DOI:
10.1002/jcp.27627
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发表时间:
2019-06-01
影响因子:
5.6
通讯作者:
Yousefi, Mehdi
Yousefi, Mehdi
中科院分区:
生物学2区
文献类型:
--
作者:
Ahmadi, Majid;Ghaebi, Mahnaz;Yousefi, Mehdi

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背景复发性流产(RM)的病因是多方面的,主要是由于染色体异常和免疫因素。RM的治疗一直是一个具有挑战性的问题,静脉注射免疫球蛋白(IVIG)在治疗RM中的作用仍有争议。材料与方法观察RM患者接受IVIG治疗后NK细胞频率和细胞毒活性的变化。共有78名有三次或三次以上反复流产史的妇女被纳入研究,在妊娠试验阳性的情况下抽取外周血。同日,38名女性静脉注射400 mg/kg IVIG,持续每四周一次,直至妊娠第30-32周。其余40例RM患者作为未治疗对照组。然后,IVIG对RM患者治疗前后NK细胞频率、细胞毒活性以及抑制性和激活性受体表达的影响进行了评估。结果IVIG治疗后32周患者NK细胞百分率和细胞毒活性明显降低(P < 0.0001)。IVIG治疗后抑制性受体表达水平升高,而激活性受体表达水平显著降低。IVIG治疗组的妊娠结局(86.8%)显著高于对照组(45%; p = 0.0006)。结论IVIG对RM患者有一定的治疗作用,外周血NK细胞的频率和功能状态可作为疗效的预测指标。
Background Recurrent miscarriage (RM) has a multifactorial etiology mainly due to chromosomal abnormalities and immunological factors. Treating RM has remained to be a challenging issue and the role of intravenous immunoglobulin (IVIG) in treating RM is still controversial. Materials and Methods This study aimed to evaluate the changes in natural killer (NK) cells' frequency and cytotoxicity in patients with RM who received the IVIG therapy. A total of 78 women with a history of three or more recurrent miscarriages were included and their peripheral blood was drawn in case of positive pregnancy test. On the same date, 400 mg/kg of IVIG was administrated intravenously in 38 women and it continued every four weeks through weeks 30-32 of gestation. The remaining 40 patients with RM were included to be the untreated control group. Then, the effects of IVIG on NK cell frequency, cytotoxic activity, and the expression of inhibitory and activating receptors in the patients with RM, pre and posttreatment were assessed. Results NK cells percentage and cytotoxicity were significantly reduced in the IVIG-treated patients after 32 weeks of gestation (p < 0.0001). Expression levels of inhibitory receptors was increased, however, the expression levels of activating receptors were significantly decreased after the IVIG therapy. Pregnancy outcome after the treatment was significantly higher (86.8%) in the IVIG-treated patients than controls (45%; p = 0.0006). Conclusion Our results suggested that women with RM may benefit from IVIG as a therapeutic approach and the frequency and functional status of peripheral NK cells may serve as a valuable predictive factor of therapy response.