A road map from single-cell transcriptome to patient classification for the immune response to trauma.

Immune dysfunction is an important factor driving mortality and adverse outcomes after trauma but remains poorly understood, especially at the cellular level. To deconvolute the trauma-induced immune response, we applied single-cell RNA sequencing to circulating and bone marrow mononuclear cells in injured mice and circulating mononuclear cells in trauma patients. In mice, the greatest changes in gene expression were seen in monocytes across both compartments.

Quality Control Measures and Validation in Gene Association Studies: Lessons for Acute Illness.

Acute illness is a complex constellation of responses involving dysregulated inflammatory and immune responses, which are ultimately associated with multiple organ dysfunction. Gene association studies have associated single-nucleotide polymorphisms (SNPs) with clinical and pharmacological outcomes in a variety of disease states, including acute illness. With approximately 4 to 5 million SNPs in the human genome and recent studies suggesting that a large portion of SNP studies are not reproducible, we suggest that the ultimate clinical utility of SNPs in acute illness depends on validation and quality control measures.

An Aging-Related Single-Nucleotide Polymorphism is Associated With Altered Clinical Outcomes and Distinct Inflammatory Profiles in Aged Blunt Trauma Patients.

The contribution of individual genetic determinants of aging to the adverse clinical outcomes and altered inflammation mediator networks characteristic of aged trauma patients is unknown. The AA genotype of the aging-related single-nucleotide polymorphism (SNP) rs2075650 in TOMM40 has been associated with longevity, while the AG and GG genotypes are associated with an increased risk of Alzheimer disease. Here, we studied the effect of rs2075650 on clinical outcomes and dynamic biomarker patterns after traumatic injury.

A conceptual time window-based model for the early stratification of trauma patients.

Progress in the testing of therapies targeting the immune response following trauma, a leading cause of morbidity and mortality worldwide, has been slow. We propose that the design of interventional trials in trauma would benefit from a scheme or platform that could support the identification and implementation of prognostic strategies for patient stratification. Here, we propose a stratification scheme based on defined time periods or windows following the traumatic event.

Young and Aged Blunt Trauma Patients Display Major Differences in Circulating Inflammatory Mediator Profiles after Severe Injury.

Background: Aging is accompanied by alterations in immune functions. How these changes translate into levels of circulating inflammatory mediators and network expression after severe trauma is not well characterized. To address this, we compared time-dependent changes in the levels of an extensive biomarker panel in cohorts of severely injured young and aged adults.