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New frontiers in precision medicine for sepsis-induced immunoparalysis

ABSTRACT Introduction: In the last decade, the sepsis research field has shifted focus from targeting hyperinflammation to reversing sepsis-induced immunoparalysis. Sepsis-induced immunoparalysis is very heterogeneous: the magnitude and the nature of the underlying immune defects differ considerably between patients, but also within individuals over time. Therefore, a ‘one-treatment-fits-all’ strategy for sepsis-induced immunoparalysis is bound to fail, and an individualized ‘precision medicine’ approach is required. Such a strategy is nevertheless hampered by the unsuitability of the currently available markers to identify the many immune defects that can manifest in individual patients. Areas covered: We describe the currently available markers for sepsis-induced immunoparalysis and limitations pertaining to their use. Furthermore, future prospects and caveats are discussed, focusing on ‘omics’ approaches: genomics, transcriptomics, epigenomics, and metabolomics. Finally, we present a contemporary overview of adjuvant immunostimulatory therapies. Expert opinion: The integration of multiple omics techniques offers a systems biology approach which can yield biomarker profiles that accurately and comprehensively gauge the extent and nature of sepsis-induced immunoparalysis. We expect this development to be instrumental in facilitating precision medicine for sepsis-induced immunoparalysis, consisting of the application of targeted immunostimulatory therapies and follow-up measurements to monitor the response to treatment and to titrate or adjust medication.