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Evaluating host responses to diagnose infection

Comparison of host immune responses in vivo versus ex vivo lipopolysaccharide stimulation in humans using an immune transcriptomic profiling panel

April 18 • P0458

D. M. Tawfik1/2, J. M. Lankelma3, L. Vachot1/2, E. Cerrato1/2, A. Pachot2, W. Joost Wiersinga4, J. Textoris1/2/5

1) EA 7426 Pathophysiology of Injury-Induced Immunosuppression, PI3, Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux, Lyon, France
2) Medical Diagnostic Discovery Department (MD3), bioMérieux S.A, Lyon, France
3) Department of Medical Microbiology and Infection Control, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam UMC, location, Amsterdam, The Netherlands
4) Division of Infectious Diseases, Department of Medicine, Amsterdam UMC, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
5) Anaesthesia and Critical Care Medicine Department, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France

Background: Patients that suffer from sepsis exhibit an early hyper-inflammatory immune response which can lead to organ failure and death. In our study, we assessed the immune modulation in the human in vivo endotoxemia model and compared it to ex vivo LPS stimulation using 38 transcriptomic markers.

Methods: Eight volunteers were challenged with intravenous LPS in vivo. In parallel, blood from another 8 volunteers was challenged ex vivo. Blood was collected before and after 4 hours of LPS challenge and tested with the Immune Profiling Panel (IPP) using the BIOFIRE® FILMARRAY® system.

Results: The use of IPP showed that markers from the innate immunity dominated the response to LPS in vivo, mainly markers related to monocytes and neutrophils. Comparing the two models, in vivo and ex vivo, revealed that most of the markers were modulated in a similar pattern (68%). Some cytokine markers such as TNF, IFN-γ and IL-1β were under-expressed ex vivo compared to in vivo. T-cell markers were either unchanged or up-modulated ex vivo, compared to a down-modulation in vivo. Interestingly, markers related to neutrophils were expressed in opposite directions, which might be due to the presence of cell recruitment and feedback loops in vivo.

Conclusions: In both models, the majority of IPP markers showed similar patterns of expression post-LPS challenge, except for several markers related to neutrophils and T-cells. The IPP tool was able to capture the early immune response in the human in vivo endotoxemia model, which is a translational model mimicking the immune response observed in septic patients.

filmarray

Immune Profiling Panel (IPP)

Paper poster