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Markers and scores for sepsis

The REAnimation Low Immune Status Markers study: phenotypic and functional alterations of adaptive immune response in critically ill patients

April 20 • P3058

V. Moucadel1, F. Venet1, J. Textoris1, S. Blein1, ML. Rol2, B. Canard2, P. Cortez3, C. Tipple4, M. Lazou5, A. Griffiths6, E. Peronnet1, A. Pachot1, G. Monneret1, T. Rimmelé1, on behalf of the REALISM study group

1) EA 7426 Pathophysiology of Injury-Induced Immunosuppression, Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux, Joint Research Unit HCL-bioMérieux, Immunology Laboratory & Anesthesia and Critical Care Medicine Department, Edouard Herriot Hospital, Lyon, France
2) BIOASTER Technology Research Institute, Lyon, France
3) Sanofi Aventis R&D, Chilly-Mazarin, France
4) GlaxoSmithKline, Cambridge, United Kingdom
5) Sanofi-Pasteur SA, Lyon, France
6) ESPCI Paris, PSL Research University, Paris, France

Background: Immune response to sepsis is complex and dynamic. Several alterations of the adaptive immune response have been already described and some even observed in other severe injuries like trauma. However, the comprehensive description of phenotypic and functional immune alterations development over time in a large cohort of patients has never been done. In addition, it is not known whether these alterations depend on the type of injury (infectious vs sterile) and if they are associated with an increased risk of deleterious outcomes.

Materials/methods: A prospective longitudinal, single-center observational study was set up in Edouard Herriot Hospital (Lyon, France) between December 2015 and March 2018. A total of 354 ICU patients suffering from sepsis, severe trauma or after major surgery, and 175 healthy volunteers were enrolled. Blood specimens were collected once from volunteers and three times from patients during the first week of ICU stay. The adaptive response was measured by concomitantly assessing cellular phenotypes (circulating lymphocyte subpopulations) and functions (proliferation, cytokine production), and mRNA levels (CD3D, CD127, PD-1) with standardized tests.

Results: Injury-induced adaptive immune profile was similar in the 3 groups of patients and characterized by a major decrease in the number of circulating effector cells affecting every lymphocyte sub-population except for regulatory T cells. Remaining circulating T cells were dysfunctional as illustrated by their decreased effector responses ex vivo. Intensity of these injury-induced alterations was maximal at D1 and decreased overtime. The persistence at the end of the first week after injury of profound lymphocyte alterations measured by the decreased CD3D mRNA level was associated with an increased risk of death and an increased risk of secondary infections independently of exposure to invasive devices.

Conclusions: Our results show that the adaptive immune response induced after injury is not dependent on the type of injury and is characterized by major alterations of T cell number and functions that are present from D1 in patients. When persisting, they are associated with deleterious outcomes in accordance with the development of delayed injury-acquired immunodeficiency. Our data support the rational for an immune intervention to restore functional immune response in these patients.

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