The REAnimation Low Immune Status Markers (REALISM) project: a protocol for broad characterisation and follow-up of injury-induced immunosuppression in intensive care unit (ICU) critically ill patients.
INTRODUCTION
The host response to septic shock is dynamic and complex. A sepsis-induced immunosuppression phase has recently been acknowledged and linked to bad outcomes and increased healthcare costs. Moreover, a marked suppression of the immune response has also been partially described in patients hospitalized in intensive care unit (ICU) for severe trauma or burns. It has been hypothesized that immune monitoring could enable identification of patients who might most benefit from novel, adjunctive immune-stimulating therapies. However, there is currently neither a clear definition for such injury-induced immunosuppression nor a stratification biomarker compatible with clinical constraints.


METHODS AND ANALYSIS
We set up a prospective, longitudinal single-centre clinical study to determine the incidence, severity and persistency of innate and adaptive immune alterations in ICU patients. We optimized a workflow to describe and follow the immunoinflammatory status of 550 patients (septic shock, severe trauma/burn and major surgery) during the first 2 months after their initial injury. On each time point, two immune functional tests will be performed to determine whole-blood TNF-α production in response to ex vivo lipopolysaccharide stimulation and the T lymphocyte proliferation in response to phytohaemagglutinin. In addition, a complete immunophenotyping using flow cytometry including monocyte HLA-DR expression and lymphocyte subsets will be obtained. New markers (ie, levels of expression of host mRNA and viral reactivation) will be also evaluated. Reference intervals will be determined from a cohort of 150 age-matched healthy volunteers. This clinical study will provide, for the first time, data describing the immune status of severe ICU patients over time.


ETHICS AND DISSEMINATION
Ethical approval has been obtained from the institutional review board (no 69HCL15_0379) and the French National Security agency for drugs and health-related products. Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals.


TRIAL REGISTRATION NUMBER
Clinicaltrials.gov Registration number: NCT02638779. Pre-results.
['Rol|Mary-Luz|ML|', 'Venet|Fabienne|F|', 'Rimmele|Thomas|T|', 'Moucadel|Virginie|V|', 'Cortez|Pierre|P|', 'Quemeneur|Laurence|L|', 'Gardiner|David|D|', 'Griffiths|Andrew|A|', 'Pachot|Alexandre|A|', 'Textoris|Julien|J|0000-0002-3821-9337', 'Monneret|Guillaume|G|', '|||']
D056704:Adaptive Immunity D000328:Adult D000368:Aged D000369:Aged, 80 and over D015415:Biomarkers D049109:Cell Proliferation D002478:Cells, Cultured D000068456:Clinical Studies as Topic D016638:Critical Illness D005260:Female D006801:Humans D007108:Immune Tolerance D007113:Immunity, Innate D016130:Immunophenotyping D007362:Intensive Care Units D008070:Lipopolysaccharides D008137:Longitudinal Studies D008297:Male D008875:Middle Aged D010937:Plant Growth Regulators D011446:Prospective Studies D012107:Research Design D012772:Shock, Septic D013514:Surgical Procedures, Operative D013601:T-Lymphocytes D014409:Tumor Necrosis Factor-alpha D014947:Wounds and Injuries D055815:Young Adult
Injury-induced immunosuppression Intensive care unit Biomarkers Adaptive immunity Healthcare-associated infections Innate immunity