4.6 Article

Association of Plasma Levels of Fas Ligand with Severity and Outcome of Sepsis

Journal

SHOCK
Volume 56, Issue 4, Pages 544-550

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/SHK.0000000000001753

Keywords

Biomarker; Fas ligand protein; necroptosis; RIPK 3 protein; sepsis

Funding

  1. Samsung Medical Center grant [SMO1200431]
  2. National Research Foundation of Korea [2020R1C1C1013557]
  3. National Research Foundation of Korea [2020R1C1C1013557] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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The study found that elevated levels of Fas ligand were associated with the severity and mortality of sepsis, but not correlated with RIPK3 levels.
Introduction: Levels of the apoptosis regulator Fas ligand (FasL) are associated with severity of sepsis, but its association with the mortality of sepsis and necroptosis, a regulated cell death mechanism, is not yet clear. We aimed to assess the association of FasL level with outcomes of sepsis and receptor interacting protein kinase-3 (RIPK3), an essential necroptosis mediator, for determining the relationship between FasL and necroptosis. Methods: Plasma FasL and RIPK3 levels were measured by ELISA from prospectively enrolled critically ill adult patients. The best cut-off level of FasL for 28-day mortality prediction was determined by Youden's index. The association between plasma levels of FasL and RIPK3 was assessed by a linear regression method. Results: Among 188 patients, 58 (30.9%) were diagnosed with sepsis and 84 (44.7%) with septic shock, respectively. Plasma levels of FasL increased in the group order of control, sepsis, and septic shock groups (P for trend < 0.001). For 142 patients with sepsis, organ dysfunction and septic shock were more prevalent in the group with plasma FasL levels that were higher than the best cut-off level. A significant difference in mortality between high and low FasL patients was observed up to 90 days (Log-rank P = 0.013). FasL levels did not significantly change over day 3 and day 7. FasL levels were not correlated with those of RIPK3. Conclusions: The plasma level of FasL was associated with severity of sepsis and was predictive of mortality. However, it was not correlated with RIPK3 level.

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