Sorbonne Université, INSERM, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), Paris, France.
Assistance Publique Hôpitaux de Paris (APHP), Hôpital Saint Antoine, Department of Geriatrics, Paris, France.
Front Immunol. 2020 Sep 18;11:571759. doi: 10.3389/fimmu.2020.571759. eCollection 2020.
Hip fracture (HF) is common in the geriatric population and is associated with a poor vital and functional prognosis which could be impacted by immunological changes. The objective here is to decipher immune changes occurring in the 1st days following HF and determine how phenotype, function, and regulation of innate and adaptive compartments adapt during acute stress event. We included HF patients, aged over 75 years. For each patient, blood samples were taken at five different timepoints: four in the perioperative period (day 0 to hospital discharge) and one at long term (6-12 months). Phenotypical and functional analysis were performed longitudinally on fresh blood or cryopreserved PBMCs. Clinical data were prospectively collected. One-hundred HF patients and 60 age-matched controls were included. Innate compartment exhibits pro-inflammatory phenotypes (hyperleukocytosis, increase of CD14+ CD16+ proportion and CCR2 expression), maintaining its ability to produce pro-inflammatory cytokines. Adaptive compartment extends toward a transitory immunosuppressive profile (leucopenia) associated with an active T-cell proliferation. Furthermore, increases of LAG-3 and PD-1 and a decrease of 2-B4 expression are observed on T-cells, reinforcing their transitory suppressive status. Of note, these immune changes are transitory and sequential but may participate to a regulation loop necessary for homeostatic immune control at long term. HF is associated with several transitory immunological changes including pro-inflammatory phenotype in innate compartment and immunosuppressive profile in adaptive compartment. A comprehensive assessment of immune mechanisms implicated in the patient's prognosis after HF could pave the way to develop new immune therapeutics strategies.
髋部骨折(HF)在老年人群中很常见,与预后不良的生命和功能相关,而免疫变化可能会影响预后。本研究旨在阐明 HF 后第 1 天发生的免疫变化,并确定固有和适应性免疫成分的表型、功能和调节在急性应激事件中如何适应。我们纳入了年龄在 75 岁以上的 HF 患者。对每位患者,在五个不同时间点采集血液样本:围手术期内(从第 0 天到出院)采集 4 次,长期(6-12 个月)采集 1 次。对新鲜血液或冷冻 PBMC 进行纵向表型和功能分析。前瞻性收集临床数据。共纳入 100 例 HF 患者和 60 名年龄匹配的对照者。固有免疫成分表现出促炎表型(白细胞增多、CD14+CD16+比例增加和 CCR2 表达增加),保持产生促炎细胞因子的能力。适应性免疫成分扩展为短暂的免疫抑制表型(白细胞减少),与 T 细胞的活性增殖相关。此外,T 细胞上观察到 LAG-3 和 PD-1 的增加以及 2-B4 表达的减少,进一步证实了它们的短暂抑制状态。值得注意的是,这些免疫变化是短暂的和连续的,但可能参与了长期维持免疫稳态的调节环路。HF 与多种短暂的免疫变化相关,包括固有免疫成分中的促炎表型和适应性免疫成分中的免疫抑制表型。全面评估 HF 后患者预后相关的免疫机制可能为开发新的免疫治疗策略铺平道路。