Sepsis, an acute and life-threatening syndrome, emerges from a dysregulated immune response to infection, leading to organ dysfunction. In Germany, over 200 individuals succumb to sepsis daily, while more than triple that number grapple with its effects. Alarmingly, even post-acute phase and after discharge, nearly 30% of patients face mortality within the first year after sepsis. This establishes sepsis as one of the leading causes of death in Germany, especially in intensive care units, despite decades of research and tens of thousands of publications. Notably, the singular causative therapy still remains antibiotic treatment.
The enduring challenge in reducing sepsis mortality lies in its intricate heterogeneity. Sepsis is most likely made up of different sub-phenotypes. In addition to these phenotypes sepsis is influenced by genetic, epigenetic, and environmental factors, and is further shaped by the dynamic interplay between pathogens and the host's immune system. Recent discourse in sepsis research emphasizes the need for precision medicine and enriched patient cohorts. While some studies use established biomarkers like IL-6 or NFκB genotypes to identify "hyper-inflammatory" states necessitating immune modulation, translating such findings into clinical therapies remains elusive.
The multifaceted nature of sepsis calls for not just new biomarkers but an entirely novel class. Despite exhaustive examinations of genetics, epigenetics, and the proteome, the interactome—comprising protein activity states and interactions—has been largely overlooked. Understanding the functionality of proteins becomes paramount when probing the immune system's status and tailoring therapeutic approaches to individual patients.
This paradigm shift towards novel biomarkers offers a transformative opportunity. It can help to better understand sepsis pathology, enable robust sepsis phenotyping, and assemble enriched patient cohorts tailored for specific therapeutic interventions. The integration of protein interactome data promises a more nuanced understanding of sepsis, laying the foundation for a breakthrough in precision medicine for this critical medical condition.