Whole blood RNA sequencing reveals a unique transcriptomic profile in patients with ARDS following hematopoietic stem cell transplantation

Joshua A Englert,Diana Barragan-Bradford,Rebecca M Baron,Laura E Fredenburgh,Paul B Dieffenbach,Joseph H Antin,Ami S Bhatt,Andrew E Lamb,Maria C Basil,Judie A Howrylak,Mayra Pinilla Vera,Angelica Higuera,Maya Shumyatcher,Michael H Cho,Robert J Soiffer,Colleen Isabelle,Blanca E Himes,Joyce B Kang,Vincent T Ho

doi:10.1186/s12931-019-0981-6

Abstract

BackgroundThe acute respiratory distress syndrome (ARDS) is characterized by the acute onset of hypoxemia and bilateral lung infiltrates in response to an inciting event, and is associated with high morbidity and mortality. Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk for ARDS. We hypothesized that HSCT patients with ARDS would have a unique transcriptomic profile identifiable in peripheral blood compared to those that did not undergo HSCT.MethodsWe isolated RNA from banked peripheral blood samples from a biorepository of critically ill ICU patients. RNA-Seq was performed on 11 patients with ARDS (5 that had undergone HSCT and 6 that had not) and 12 patients with sepsis without ARDS (5 that that had undergone HCST and 7 that had not).ResultsWe identified 687 differentially expressed genes between ARDS and ARDS-HSCT (adjusted p-value < 0.01), including IFI44L, OAS3, LY6E, and SPATS2L that had increased expression in ARDS vs. ARDS-HSCT; these genes were not differentially expressed in sepsis vs sepsis-HSCT. Gene ontology enrichment analysis revealed that many differentially expressed genes were related to response to type I interferon.ConclusionsOur findings reveal significant differences in whole blood transcriptomic profiles of patients with non-HSCT ARDS compared to ARDS-HSCT patients and point toward different immune responses underlying ARDS and ARDS-HSCT that contribute to lung injury.

Highlights

The acute respiratory distress syndrome (ARDS) is characterized by the acute onset of hypoxemia and bilateral lung infiltrates in response to an inciting event, and is associated with high morbidity and mortality
ARDS is a syndrome with high morbidity and mortality characterized by the acute onset of bilateral lung infiltrates and hypoxemia that frequently results in acute respiratory failure [1]
None of the ARDS subjects were treated with neuromuscular blockade or prone positioning at the time the blood sample used for RNA sequencing was collected

Summary

Introduction

The acute respiratory distress syndrome (ARDS) is characterized by the acute onset of hypoxemia and bilateral lung infiltrates in response to an inciting event, and is associated with high morbidity and mortality. ARDS is a syndrome with high morbidity and mortality characterized by the acute onset of bilateral lung infiltrates and hypoxemia that frequently results in acute respiratory failure [1]. One barrier to developing effective therapies is that ARDS is a heterogeneous syndrome that encompasses a wide variety of patients with lung injury from many different causes. Several studies have used clinical data and previously identified biomarkers to define several ARDS subphenotypes with distinct clinical outcomes, inflammatory profiles, and response to ARDS therapies [3, 7, 8] underscoring the need for a better understanding of these different populations

Methods

Results

Discussion

Conclusion