Extracorporeal photopheresis induces NETosis in neutrophils derived from patients with chronic graft-vs-host disease

IF 1.4 4区医学 Q4 HEMATOLOGY

Journal of Clinical Apheresis Pub Date : 2023-07-13 DOI:10.1002/jca.22073

Idan Goldberg, Galit Granot, Alona Telerman, Shirly Partouche, Tzippy Shochat, Erez Halperin, Anat Gafter-Gvili, Liat Shargian, Moshe Yeshurun, Pia Raanani, Ofir Wolach, Vered Yahalom

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引用次数: 0

Abstract

Introduction

Extracorporeal photopheresis (ECP) is considered an effective treatment for patients with chronic graft vs host disease (cGVHD) and demonstrates efficacy in ameliorating GVHD. The mechanism by which ECP acts against cGVHD is not fully understood. Preliminary observations have hinted at the potential involvement of neutrophil extracellular traps (NETs) formation in the pathogenesis of cGVHD. We aimed to assess the influence of ECP on the formation of NETs in patients with cGVHD as a potential mechanism in this setting.

Methods

Patients treated with ECP for cGVHD at the Rabin Medical Center were included in this study. Blood samples were obtained at three different time points: before starting an ECP cycle, at the end of the first day of treatment, and 24 h following the initiation of the ECP treatment cycle. Neutrophils were harvested from all blood samples. NET formation was assessed by measurement of NET-bound specific neutrophil elastase activity and by immunofluorescence staining.

Results

Six patients (two females and four males) with cGVHD were included in the study. We observed a significant increase in NET formation among all six patients following ECP. Net-bound specific neutrophil elastase activity was elevated from a median value of 2.23 mU/mL (interquartile range [IQR] 2.06-2.47 mU/mL) at baseline to a median value of 13.06 mU/mL (IQR 10.27-15.97 mU/mL) immediately after the treatment and to a peak median value of 14.73 mU/mL (IQR 9.6-22.38 mU/mL) 24 h following the initiation of the ECP cycle. A qualitative assessment of NET formation using immunofluorescence staining has demonstrated markedly increased expression of citrullinated histone H3, a marker of NET formation, following ECP treatment.

Conclusions

Our preliminary data indicate that ECP induces NET formation among patients with cGVHD. The contribution of increased NET formation to the therapeutic effect of cGVHD should be further investigated.

Abstract Image

查看原文本刊更多论文

体外光分离诱导来自慢性移植物抗宿主病患者的中性粒细胞NETosis。

引言：体外光合疗法（ECP）被认为是治疗慢性移植物抗宿主病（cGVHD）患者的有效方法，并在改善移植物抗逆转录病毒方面显示出疗效。ECP对抗cGVHD的机制尚不完全清楚。初步观察提示中性粒细胞外陷阱（NETs）的形成可能参与cGVHD的发病机制。我们旨在评估ECP对cGVHD患者NETs形成的影响，这是这种情况下的一种潜在机制。方法：本研究纳入在拉宾医疗中心接受ECP治疗的cGVHD患者。在三个不同的时间点采集血样：ECP周期开始前、治疗第一天结束时和24 h。从所有血液样本中采集中性粒细胞。通过测量NET结合的特异性中性粒细胞弹性蛋白酶活性和免疫荧光染色来评估NET的形成。结果：6名cGVHD患者（2名女性和4名男性）被纳入研究。我们观察到ECP后所有6名患者的NET形成显著增加。净结合特异性中性粒细胞弹性蛋白酶活性从中值2.23升高 mU/mL（四分位间距[IQR]2.06-2.47 mU/mL）至13.06的中值 mU/mL（IQR 10.27-15.97 mU/mL），并达到14.73的峰值中值 mU/mL（IQR 9.6-22.38 mU/mL）24 h。使用免疫荧光染色对NET形成进行的定性评估表明，ECP处理后，瓜氨酸组蛋白H3（NET形成的标志物）的表达显著增加。结论：我们的初步数据表明ECP在cGVHD患者中诱导NET的形成。NET形成增加对cGVHD治疗效果的贡献有待进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Apheresis 医学-血液学

CiteScore

2.80

自引率

13.30%

发文量

审稿时长

>12 weeks

期刊介绍： The Journal of Clinical Apheresis publishes articles dealing with all aspects of hemapheresis. Articles welcomed for review include those reporting basic research and clinical applications of therapeutic plasma exchange, therapeutic cytapheresis, therapeutic absorption, blood component collection and transfusion, donor recruitment and safety, administration of hemapheresis centers, and innovative applications of hemapheresis technology. Experimental studies, clinical trials, case reports, and concise reviews will be welcomed.