Hip Fracture Leads to Transitory Immune Imprint in Older Patients.

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.

Elevated Neopterin Levels Predict Early Death in Older Hip-fracture Patients.

Our society faces a major challenge concerning management of the health and socio-economic burden caused by acute physical stress in the older population (+75years). In particular, hip-fracture surgery (HFS) represents a major health care preoccupation, affecting 1.6 million patients worldwide, resulting in a significant drop in life quality and autonomy. The trauma is associated with 20-30% one-year mortality in the elderly. In the present study, we aim to identify factors, which influence and/or predict the outcome of elderly hip- fracture patients (HFP) post-surgery. Our objective was to identify biomarkers with a prognostic capacity of one-year mortality. We employed an observational cohort of HFP (n=60) followed-up longitudinally during the first year post fracture. Clinical and biological data (n=136), collected at arrival to hospital, were then compared to healthy controls (n=42) and analyzed using a regularized logistic regression model with lasso penalty followed by 10-fold cross-validation of variables. We show that plasmatic neopterin levels, a molecule released by IFN-γ-activated macrophages, is predictive of mortality in HFP (ROC-AUC=0.859). Moreover, neopterin measured at arrival to the hospital correlated negatively with the time of survival after HFS. Neopterin therefore represents a biomarker, which enables better follow-up of patients at risk of early death.

Coordinated expansion of both memory T cells and NK cells in response to CMV infection in humans.

NK cells are key players in the fight against persistent viruses. Human cytomegalovirus (HCMV) infection is associated with the presence of a population of CD16(+) CD56(dim) NKG2C(+) NK cells in both acutely and latently infected individuals. Here, we studied the nature of these terminally differentiated NK cells in different human populations infected with HCMV: healthy donors stratified by age, thymectomized individuals, pregnant women suffering from primary CMV infection, and lung transplant patients. Both CD16(+) CD56(dim) NK- and CD8 T-cell phenotypes as well as functional capacities were determined and stratified according to age and/or CMV event. Similarly to T-cell responsiveness, we observe an accumulation over time of NKG2C(+) NK cells, which preferentially expressed CD57. This accumulation is particularly prominent in elderly and amplified further by CMV infection. Latent HCMV infection (without replication) is sufficient for NKG2C(+) CD57(+) NK cells to persist in healthy individuals but is not necessarily required in old age. Collectively, the present work supports the emerging concept that CMV shapes both innate and adaptive immunity in humans.