Hip Fracture Leads to Transitory Immune Imprint in Older Patients

Abstract

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.

Decoding the immune landscape following hip fracture in elderly patients: unveiling temporal dynamics through single-cell RNA sequencing

“…Among them, monocytes are of particular interest because they express inflammatory genes mainly in PBMCs [ 34 , 35 ]. In elderly hip fracture patients, the frequencies of postoperative monocyte increased significantly within 24 h, gradually returning to normal level by day 7, which is consistent with other findings [ 36 ]. C-Mono2 subsets exhibit high expression levels of S100 family genes, which are predominantly expressed by neutrophils and monocytes and play a crucial role in inflammation development [ 37 ].…”

IL-7 producing immunotherapy improves ex vivo T cell functions of immunosenescent patients, especially post hip fracture

“…This cohort was described previously. 9 For immunosenescence status comparison, 5 young donors (25< age <40) from blood transfusion center (Etablissement Français du Sang) were also included (CTRLy).…”

“… 7 , 8 The trauma induced by HF is also associated with additional immunological changes such as a transient pro-inflammatory phenotype of the innate compartment and immunosuppressive profile of the adaptative compartment. 9 These changes may participate in the poor medical outcome post-HF in some of these patients. A comprehensive investigation of the induced immune-alterations post-stress would open avenues for the development of immunotherapies enabling the restoration of immune homeostasis, especially in the situation of trauma such as HF.…”

“… 32 Hence, impact of the MVA-hIL-7-Fc and more specifically of the expressed hIL-7-Fc on T cells of elderly immunosenescent patients suffering from HF trauma was investigated. Peripheral Blood Mononuclear Cells (PBMCs) from the HIPAGE cohort, 9 which includes HF patients and age-matched controls, were ex vivo stimulated using the MVA produced hIL-7-Fc and impacts on T cell phenotypes and functions were analyzed.…”

The promising roles of macrophages in geriatric hip fracture

“…Reduced quality of life, subsequent secondary fracture and heavy financial burdens make HF an increasingly important public health concern for elderly individuals. Healthy older individuals experience higher levels of stress than young adults, and HF in elderly patients is associated with complicated immunological changes, including changes in innate proinflammatory phenotypes and adaptive immunosuppressive responses (Vallet et al, 2020). In addition, studies have shown that geriatric HF patients have a reduced ability to exhibit an effective antimicrobial immune response and that these immunological effects can be sustained until 7 days after surgery (Sutherland et al, 2015).…”