Burn Injury Induces Proinflammatory Plasma Extracellular Vesicles That Associate with Length of Hospital Stay in Women: CRP and SAA1 as Potential Prognostic Indicators.

Robert Maile,Micah L Willis,Cressida Mahung,Alex Prevatte,Laura E Herring,Bruce Cairns,Shannon Wallet,Leon G Coleman

doi:10.3390/ijms221810083

Abstract

Severe burn injury is a devastating form of trauma that results in persistent immune dysfunction with associated morbidity and mortality. The underlying drivers of this immune dysfunction remain elusive, and there are no prognostic markers to identify at-risk patients. Extracellular vesicles (EVs) are emerging as drivers of immune dysfunction as well as biomarkers. We investigated if EVs after burn injury promote macrophage activation and assessed if EV contents can predict length of hospital stay. EVs isolated early from mice that received a 20% total body surface area (TBSA) burn promoted proinflammatory responses in cultured splenic macrophages. Unbiased LC-MS/MS proteomic analysis of early EVs (<72 h post-injury) from mice and humans showed some similarities including enrichment of acute phase response proteins such as CRP and SAA1. Semi-unbiased assessment of early human burn patient EVs found alterations consistent with increased proinflammatory signaling and loss of inhibition of CRP expression. In a sample of 50 patients with large burn injury, EV SAA1 and CRP were correlated with TBSA injury in both sexes and were correlated with length of hospital stay in women. These findings suggest that EVs are drivers of immune responses after burn injury and their content may predict hospital course.

Highlights

We investigated if circulating Extracellular vesicles (EVs) that are released early after burn injury promote immune dysfunction and could be used as biomarkers to identify atrisk patients
We found some commonalities between the components in both human and mouse EVs, such as the acute phase response (APR) protein Serum amyloid A-1 (SAA1) and increases in circulating complement/coagulation factors
We found that neither C-reactive protein (CRP) nor SAA1 in EV-depleted plasma was associated with severity of burn injury or length of hospital stay

Summary

Introduction

Deaths from burn injury are commonly caused by immune-related sequelae such as pneumonia, organ failure and other opportunistic bacterial infections. These occur days to weeks after repair of the skin barrier function by surgical skin grafting, implicating chronic immune dysfunction. The acute phase (0–72 h post-injury), referred to as the burn shock or systemic inflammatory response syndrome (SIRS), results in widespread barrier dysfunction and multiple organ failure. During this immediateearly time period, widespread tissue injury and organ damage results in robust Toll-like receptor (TLR) and cytokine signaling in macrophages (MØ) and neutrophils (NØ) [5,6,7,8]

Methods

Results

Conclusion