Tenascin C: A marker of critical illness

Research output: PhD ThesisPhD-Thesis - Research and graduation internal

Abstract

Sepsis is a life-threatening condition, characterized by organ dysfunction and a dysregulated host response to infection. Despite having been a major cause of intensive care unit (ICU) mortality for decades, our understanding of its pathophysiology is still limited. However, positive feedback loops, where tissue damage leads to the release of pro-inflammatory signalling which in turn causes more tissue damage, seem to play an important role. In this thesis, we study the role of two potential biomarkers that may contribute to this: Tenascin C (TNC) and Trefoil Factor 3 (TFF3). Part I focusses on the association of TNC and TFF3 with the clinical presentation and outcomes of critically ill patients. Part II consists of pre-clinical studies into the functional role of TNC during pneumonia and pneumosepsis.
In short, we show that in patients, plasma TNC levels are associated with critical illness in general and infection specifically. During sepsis, TNC levels are driven by disease severity and do not independently associate with mortality. In contrast, TNC did independently contribute to the prediction of mortality in our cohort of ARDS patients. However, as a biomarker TNC does not perform sufficiently well to diagnose ARDS, or to distinguish infectious- versus non-infectious pulmonary disease. Likewise, plasma TFF3 is associated with abdominal sepsis and mortality, but has no added value in predicting adverse outcome. In vivo studies of the function of TNC revealed that while literature indicates TNC is an important driver of persisting inflammation in sterile models, it does not contribute greatly to innate immune function or bacterial outgrowth and clearance during bacterial pneumonia and pneumosepsis. These observations contribute to an framework emerging in literature which indicates that the function of TNC may be highly context dependent.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Other
Supervisors/Advisors
  • van der Poll, Tom, Supervisor
  • Scicluna, Brendon P., Co-supervisor
  • Uhel, Fabrice, Co-supervisor
Award date28 Jan 2022
Publication statusPublished - 2022

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