高水平的单核细胞来源的髓系抑制细胞与肺炎及伴有多器官功能衰竭的脓毒症患者的良好预后相关。
High levels of monocytic myeloid-derived suppressor cells are associated with favorable outcome in patients with pneumonia and sepsis with multi-organ failure.
作者信息
Schrijver Irene T, Karakike Eleni, Théroude Charlotte, Baumgartner Pétra, Harari Alexandre, Giamarellos-Bourboulis Evangelos J, Calandra Thierry, Roger Thierry
机构信息
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, CLED.04.407, Chemin des Boveresses 155, 1066, Epalinges, Switzerland.
4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
出版信息
Intensive Care Med Exp. 2022 Feb 11;10(1):5. doi: 10.1186/s40635-022-00431-0.
BACKGROUND
Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with immunosuppressive functions sub-classified into monocytic and polymorphonuclear MDSCs (M-MDSCs and PMN-MDSCs). Clinical studies reported increased levels of MDSCs that were associated with poor outcome in sepsis patients. Since sepsis patients exhibit signs of inflammation and immunosuppression, MDSCs may provide benefit by dampening deleterious inflammation in some patients. To test this hypothesis, we measured MDSCs in critically ill sepsis patients with pneumonia and multi-organ dysfunctions and a high likelihood of death.
METHODS
This was a prospective multicenter observational cohort study performed in eight ICUs in Athens and Thessaloniki, Greece, enrolling critically ill patients with pneumonia and sepsis with multi-organ dysfunctions. A flow cytometry approach using blood collected at study inclusion in tubes containing lyophilized antibodies combined to unsupervised clustering was developed to quantify M-MDSCs and PMN-MDSCs.
RESULTS
Forty-eight patients were included, of whom 34 died within 90 days. At study inclusion, M-MDSCs and PMN-MDSCs were increased in sepsis patients when compared to healthy subjects (3.07% vs 0.96% and 22% vs 2.1% of leukocytes, respectively; p < 10). Increased PMN-MDSCs were associated with secondary infections (p = 0.024) and new sepsis episodes (p = 0.036). M-MDSCs were more abundant in survivors than in patients who died within 28 days (p = 0.028). Stratification of patients according to M-MDSC levels revealed that high levels of M-MDSC were associated with reduced 90-day mortality (high vs low M-MDSCs: 47% vs 84% mortality, p = 0.003, hazard ratio [HR] = 3.2, 95% CI 1.4-7.2). Combining high M-MDSC levels with low Acute Physiology and Chronic Health Evaluation (APACHE) II score improved patient stratification (M-MDSCs/APACHE II vs M-MDSCs/APACHE II: 20% vs 80% 90-day mortality, p = 0.0096, HR = 7.2, 95% CI 1.6-32). In multivariate analyses high M-MDSCs remained correlated with improved survival in patients with low APACHE II score (p = 0.05, HR = 5.26, 95% CI 1.0-27.8).
CONCLUSION
This is the first study to associate high levels of M-MDSCs with improved survival in sepsis patients.
背景
髓系来源的抑制性细胞（MDSCs）是具有免疫抑制功能的未成熟髓细胞，可分为单核细胞样MDSCs和多形核MDSCs（M-MDSCs和PMN-MDSCs）。临床研究报告称，脓毒症患者体内MDSCs水平升高与预后不良相关。由于脓毒症患者表现出炎症和免疫抑制迹象，MDSCs可能通过减轻某些患者的有害炎症而带来益处。为验证这一假设，我们对患有肺炎、多器官功能障碍且死亡可能性高的重症脓毒症患者的MDSCs进行了检测。
方法
这是一项前瞻性多中心观察性队列研究，在希腊雅典和塞萨洛尼基的8个重症监护病房进行，纳入患有肺炎和脓毒症且伴有多器官功能障碍的重症患者。开发了一种流式细胞术方法，使用在研究纳入时采集于含有冻干抗体的试管中的血液，并结合无监督聚类来量化M-MDSCs和PMN-MDSCs。
结果
共纳入48例患者，其中34例在90天内死亡。在研究纳入时，与健康受试者相比，脓毒症患者的M-MDSCs和PMN-MDSCs增加（分别为白细胞的3.07%对0.96%和22%对2.1%；p < 0.01）。PMN-MDSCs增加与继发感染（p = 0.024）和新的脓毒症发作（p = 0.036）相关。M-MDSCs在幸存者中比在28天内死亡的患者中更为丰富（p = 0.028）。根据M-MDSC水平对患者进行分层显示，高水平的M-MDSC与90天死亡率降低相关（高M-MDSCs与低M-MDSCs：死亡率47%对84%，p = 0.003，风险比[HR] = 3.2，95%可信区间1.4 - 7.2）。将高M-MDSC水平与低急性生理与慢性健康状况评分系统（APACHE）II评分相结合可改善患者分层（M-MDSCs/APACHE II与M-MDSCs/APACHE II：90天死亡率20%对80%，p = 0.0096，HR = 7.2，95%可信区间1.6 - 32）。在多变量分析中，高M-MDSCs在低APACHE II评分患者中仍与生存率改善相关（p = 0.05，HR = 5.26，95%可信区间1.0 - 27.8）。
结论
这是第一项将高水平M-MDSCs与脓毒症患者生存率改善相关联的研究。
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