Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

背景：髋部骨折（HF）在老年人群中很常见，并伴有重要的生命和功能预后，可能会受到免疫学改变的影响。此处的目的是破译在HF后第一天发生的免疫变化，并确定在急性应激事件期间先天性和适应性区室的表型，功能和调节如何适应。

方法：我们纳入了75岁以上的HF患者。对于每位患者，在五个不同的时间点采集血液样本：围手术期（出院第0天）四次，长期采样（6至12个月）。对新鲜血液或冷冻保存的PBMC纵向进行表型和功能分析。前瞻性收集临床数据。

结果：包括一百名HF患者和60名年龄匹配的对照。先天区室表现出促炎性表型（白细胞增多，CD14 + CD16 +比例增加和CCR2表达），保持其产生促炎性细胞因子的能力。适应性区室延伸至与主动T细胞增殖相关的暂时性免疫抑制特征（白细胞减少）。此外，在T细胞上观察到了LAG-3和PD-1的增加以及2-B4表达的减少，从而增强了它们的短暂抑制状态。值得注意的是，这些免疫变化是暂时的和顺序的，但可能参与长期进行稳态免疫控制所必需的调节回路。

结论：HF与几种短暂的免疫学改变相关，包括先天区室的促炎表型和适应区室的免疫抑制特征。HF后涉及患者预后的免疫机制的全面评估可为开发新的免疫治疗策略铺平道路。