具有T细胞杀伤功能的循环未成熟粒细胞可预测脓毒症病情恶化*

Circulating immature granulocytes with T-cell killing functions predict sepsis deterioration*.

作者信息

Guérin Estelle, Orabona Marie, Raquil Marie-Astrid, Giraudeau Bruno, Bellier Rémy, Gibot Sébastien, Béné Marie-Christine, Lacombe Francis, Droin Nathalie, Solary Eric, Vignon Philippe, Feuillard Jean, François Bruno

机构信息

1Hematology Laboratory, Dupuytren University Hospital, Limoges, France. 2Intensive Care Unit, Dupuytren University Hospital, Limoges, France. 3Inserm UMR1009, Paris-Sud University, Gustave Roussy Institute, Villejuif, France. 4Inserm CIC-P 0202, Tours Regional University Hospital, François Rabelais, University, Tours, France. 5Intensive Care Unit, Central Hospital, Nancy, France. 6Immunology Laboratory, Brabois University Hospital, Nancy, France. 7Hematology Laboratory, Haut-Lévêque University Hospital, Pessac, France. 8Inserm CIC-P 0801, Dupuytren University Hospital, Limoges, France.

出版信息

Crit Care Med. 2014 Sep;42(9):2007-18. doi: 10.1097/CCM.0000000000000344.

DOI:10.1097/CCM.0000000000000344

PMID:24942511

Abstract

OBJECTIVES

Primary objective was to identify leukocyte subsets that could predict the early evolution of sepsis at 48 hours (i.e., deterioration or stability/improvement). Secondary objectives were to evaluate the prognostic value of leukocyte subsets on mortality and immunosuppressive properties of immature granulocytes.

DESIGN

Twenty-three peripheral blood leukocyte subsets were analyzed using a new-generation 10-color flow cytometry. T-cell killing activity of immature granulocytes was explored using a sorting method specifically developed.

SETTING

ICUs and emergency departments.

PATIENTS

All patients admitted to emergency department and ICU for sepsis ongoing for less than 24 hours were eligible. Exclusion criteria were pregnancy, age less than 18 years, solid tumors, HIV infection, hematological or inflammatory conditions, and immunosuppressive drugs. Finally, 177 patients were included.

INTERVENTIONS

None.

MEASUREMENTS AND MAIN RESULTS

The two most salient features of sepsis were decreased CD10 (CD10) and CD16 (CD16) expressions on granulocytes. With a threshold of 90% of CD10 and 15% of CD16 granulocytes, these immunophenotypic features, which are those of immature granulocytes, predicted sepsis deterioration at 48 hours with a sensitivity of 57% and 70% and a specificity of 78% and 82%, respectively. Survival rate at day 30 was 99% for patients without CD10 and CD16, 85% for patients with increased CD16 only, and 63% for patients with increased CD16 and CD10 granulocytes (p < 0.001). Among CD16 immature granulocytes, we identified a CD14/CD24 myeloid-derived suppressor cell subset with the capability of killing activated T cells. Consistently, an excess of CD16 immature granulocytes was associated with both CD3 and CD4 T-cell lymphopenia in deteriorating patients.

CONCLUSIONS

Circulating immature granulocytes predicted early sepsis deterioration and were enriched in myeloid-derived suppressor cells which could be responsible for immunosuppression through the induction of T-cell lymphopenia.

摘要

目的

主要目的是确定可预测脓毒症48小时早期演变（即病情恶化或稳定/改善）的白细胞亚群。次要目的是评估白细胞亚群对死亡率的预后价值以及未成熟粒细胞的免疫抑制特性。

设计

使用新一代10色流式细胞术分析23种外周血白细胞亚群。采用专门开发的分选方法探究未成熟粒细胞的T细胞杀伤活性。

地点

重症监护病房和急诊科。

患者

所有因脓毒症入住急诊科和重症监护病房且病程少于24小时的患者均符合条件。排除标准为妊娠、年龄小于18岁、实体瘤、HIV感染、血液学或炎症性疾病以及免疫抑制药物。最终纳入177例患者。

干预措施

无。

测量指标及主要结果

脓毒症的两个最显著特征是粒细胞上CD10（CD10）和CD16（CD16）表达降低。以90%的CD10和15%的CD16粒细胞为阈值，这些未成熟粒细胞的免疫表型特征预测脓毒症在48小时时病情恶化，敏感性分别为57%和70%，特异性分别为78%和82%。无CD10和CD16的患者30天生存率为99%，仅CD16升高的患者为85%，CD16和CD10粒细胞均升高的患者为63%（p<0.001）。在CD16未成熟粒细胞中，我们鉴定出一个具有杀伤活化T细胞能力的CD14/CD24髓源性抑制细胞亚群。一致的是，在病情恶化的患者中，过量的CD16未成熟粒细胞与CD3和CD4 T细胞淋巴细胞减少相关。