Circulating cell death biomarker TRAIL is associated with increased organ dysfunction in sepsis

Schenck, Edward J.; Kevin, C.; Price, David R.; Nicholson, Thomas; Oromendia, Clara; Gentzler, Eliza; Sánchez, Elizabeth; Baron, Rebecca M.; Fredenburgh, Laura E.; Huh, Jin Won; Siempos, Ilias I.; Choi, Augustine M.K.

doi:10.1172/jci.insight.127143

Cited by 40 publications

(38 citation statements)

References 40 publications

(52 reference statements)

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“…In certain pathologic environments, such as acidic states, TRAIL triggers necroptosis via RIPK1 and RIPK3 to hinder caspase-dependent apoptosis [ 10 , 34 ]. Our study, as well as the study by Schenck et al [ 13 ], illustrated a significant correlation between the plasma levels of TRAIL and RIPK3, proposing the possibility that TRAIL may have an impact on sepsis through the necroptosis pathway. Nonetheless, it should be noted that this correlation between the TRAIL and RIPK3 proteins may not provide direct evidence that TRAIL reflects the process of necroptosis of sepsis.…”

Section: Discussionsupporting

confidence: 82%

“…However, definite causes could not be determined. No relationship between TRAIL and mortality was observed in our cohort, in addition to another Korean cohort studied by Schenck et al [ 13 ]. This raises an ethnic difference as one of the many possibilities.…”

Section: Discussioncontrasting

confidence: 47%

“…Tian et al reported that the level of soluble TRAIL was lower in patients with septic shock (defined by an old definition) compared to healthy controls or patients with sepsis; soluble TRAIL was also associated with mortality [ 12 ]. Very recently, a multicenter study demonstrated an inverse correlation between the level of circulating TRAIL and both organ dysfunction and RIPK3; [ 13 ] however, the association of TRAIL with mortality was portrayed in only two of three cohorts. The inverse relationship between plasma TRAIL level and sepsis severity observed in our study concurs with the results of two previous studies, strengthening the growing evidence of the potential role of TRAIL in sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…Contrary to previous studies, the plasma TRAIL level was not associated with either 28-day ICU mortality or in-hospital mortality in our study. Interestingly, in the study by Schenck et al [ 13 ], the association between the plasma level of TRAIL with mortality was depicted only in two American cohorts of the United States, but not in a Korean cohort. The authors speculated that different baseline characteristics or processes of care might have contributed to this discrepancy.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study, plasma TRAIL was related to poor outcomes in patients with sepsis [ 12 ]. A subsequent multicenter study suggested a relationship between the plasma level of TRAIL with necroptosis in sepsis; however, its association with mortality demonstrated a contradictory result [ 13 ]. Therefore, further studies are necessary to clarify the relationship between plasma TRAIL and predicting outcomes of patients with sepsis.…”

Section: Introductionmentioning

confidence: 99%

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Association of Plasma Level of TNF-Related Apoptosis-Inducing Ligand with Severity and Outcome of Sepsis

Yoo

Lee

Park

et al. 2020

JCM

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Recent studies have suggested that TNF-related apoptosis-inducing ligand (TRAIL) is associated with mortality in sepsis, possibly through necroptosis. The objective of this study was to analyze the association between the plasma level of TRAIL and sepsis severity and outcomes. Furthermore, the plasma level of TRAIL was compared to that of receptor-interacting protein kinase-3 (RIPK3), a key executor of necroptosis, to identify any correlation between TRAIL and necroptosis. Plasma levels of TRAIL and RIPK3 from consecutively enrolled critically ill patients were measured by ELISA. Of 190 study patients, 59 (31.1%) and 84 (44.2%) patients were diagnosed with sepsis and septic shock, respectively. There was a trend of decreased plasma level of TRAIL across the control, sepsis, and septic shock groups. For 143 patients with sepsis, patients with low plasma TRAIL were more likely to have septic shock and higher SAPS3 and SOFA scores. However, no difference in 28-day and 90-day mortalities was observed between the two groups. The plasma level of TRAIL was inversely associated with RIPK3 in patients with sepsis. Plasma levels of TRAIL increased over time on days three and seven, and were inversely associated with sepsis severity and RIPK3 level, but not with mortality.

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Section: Discussionsupporting

confidence: 82%

Section: Discussioncontrasting

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Association of Plasma Level of TNF-Related Apoptosis-Inducing Ligand with Severity and Outcome of Sepsis

Yoo

Lee

Park

et al. 2020

JCM

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Death receptor 5 promotes tumor progression in gastric cancer

Chen,

Li,

Huangfu

et al. 2023

FEBS Open Bio

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Death receptor 5 (DR5) can inhibit malignant proliferation via TRAIL‐induced apoptosis in many cancers. Here, we examined the expression and sublocalization of DR5 in gastric cancer, as well as its effects on clinical prognosis and cellular processes. Our analysis included a cohort of 240 gastric cancer patients. Bioinformatic analysis showed a significant correlation between DR5 and DNA replication, tumor mutation burden (TMB), and tumor stemness. Unlike death receptor 4 (DR4TRAIL‐R1), DR5 was expressed in the the cytoplasm and nucleus, and was found to be positively correlated with lymphovascular invasion, lymph node metastasis, and TNM stage. Patients with positive DR5 had worse overall survival (OS) (p=0.006). The multivariate Cox model showed that DR5 is an independent poor prognostic factor (Hazard Ratio =1.693). Furthermore, knockdown of DR5 inhibited aggressive behaviors including proliferation and metastasis in gastric cancer cells, and inhibited lung metastasis in vivo. In summary, nuclear localization of DR5 expression is a poor prognosis factor in gastric cancer, and promotes growth, invasion, and metastasis of tumor cells in vitro and in vivo.

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Simultaneous detection of sepsis host response biomarkers in whole blood using electrochemical biosensor

Tanak¹,

Sardesai

Muthukumar³

et al. 2022

Bioengineering & Transla Med

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Sepsis is a silent killer, caused by a syndromic reaction of the body's immune system to an infection that is typically the ultimate pathway to mortality due to numerous infectious diseases, including COVID‐19 across the world. In the United States alone, sepsis claims 220,000 lives, with a dangerously high fatality rate between 25% and 50%. Early detection and treatment can avert 80% of sepsis mortality which is currently unavailable in most healthcare institutions. The novelty in this work is the ability to simultaneously detect eight (IL‐6, IL‐8, IL‐10, IP‐10, TRAIL, d‐dimer, CRP, and G‐CSF) heterogeneous immune response biomarkers directly in whole blood without the need for dilution or sample processing. The DETecT sepsis (Direct Electrochemical Technique Targeting Sepsis) 2.0 sensor device leverages electrochemical impedance spectroscopy as a technique to detect subtle binding interactions at the metal/semi‐conductor sensor interface and reports results within 5 min using only two drops (~100 μl) of blood. The device positively (r >0.87) correlated with lab reference standard LUMINEX for clinical translation using 40 patient samples. The developed device showed diagnostic accuracy greater than 80% (AUC >0.8) establishing excellent specific and sensitive response. Portable handheld user‐friendly feature coupled with precise quantification of immune biomarkers makes the device amenable in a versatile setting providing insights on patient's immune response. This work highlights an innovative solution of enhancing sepsis care and management in the absence of a decision support device in the continuum of sepsis care.

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Circulating cell death biomarker TRAIL is associated with increased organ dysfunction in sepsis

Cited by 40 publications

References 40 publications

Association of Plasma Level of TNF-Related Apoptosis-Inducing Ligand with Severity and Outcome of Sepsis

Association of Plasma Level of TNF-Related Apoptosis-Inducing Ligand with Severity and Outcome of Sepsis

Death receptor 5 promotes tumor progression in gastric cancer

Simultaneous detection of sepsis host response biomarkers in whole blood using electrochemical biosensor

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