Four Biomarkers Linked to Activation of Cluster of Differentiation 8-Positive Lymphocytes Predict Clinical Outcomes in Pediatric Acute Liver Failure
© 2020 by the American Association for the Study of Liver Diseases..
BACKGROUND AND AIMS: Immune dysregulation contributes to the pathogenesis of pediatric acute liver failure (PALF). Our aim was to identify immune activation markers (IAMs) in PALF that are associated with a distinct clinical phenotype and outcome.
APPROACH AND RESULTS: Among 47 PALF study participants, 12 IAMs collected ≤6 days after enrollment were measured by flow cytometry and IMMULITE assay on blood natural killer and cluster of differentiation 8-positive (CD8+ ) lymphocytes and subjected to unsupervised hierarchical analyses. A derivation cohort using 4 of 12 IAMs which were available in all participants (percent perforin-positive and percent granzyme-positive CD8 cells, absolute number of CD8 cells, soluble interleukin-2 receptor level) were sufficient to define high (n = 10), medium (n = 15), and low IAM (n = 22) cohorts. High IAM was more frequent among those with indeterminate etiology than those with defined diagnoses (80% versus 20%, P < 0.001). High IAM was associated with higher peak serum total bilirubin levels than low IAM (median peak 21.7 versus 4.8 mg/dL, P < 0.001) and peak coma grades. The 21-day outcomes differed between groups, with liver transplantation more frequent in high IAM participants (62.5%) than those with medium (28.2%) or low IAM (4.8%) (P = 0.002); no deaths were reported. In an independent validation cohort (n = 71) enrolled in a prior study, segregation of IAM groups by etiology, initial biochemistries, and short-term outcomes was similar, although not statistically significant. High serum aminotransferases, total bilirubin levels, and leukopenia at study entry predicted a high immune activation profile.
CONCLUSION: Four circulating T-lymphocyte activation markers identify a subgroup of PALF participants with evidence of immune activation associated with a distinct clinical phenotype and liver transplantation; these biomarkers may identify PALF participants eligible for future clinical trials of early targeted immunosuppression.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:73 |
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| Enthalten in: |
Hepatology (Baltimore, Md.) - 73(2021), 1 vom: 01. Jan., Seite 233-246 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Leonis, Mike A [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers |
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| Anmerkungen: |
Date Completed 18.06.2021 Date Revised 23.10.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/hep.31271 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM308791681 |
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| 100 | 1 | |a Leonis, Mike A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Four Biomarkers Linked to Activation of Cluster of Differentiation 8-Positive Lymphocytes Predict Clinical Outcomes in Pediatric Acute Liver Failure |
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| 500 | |a Date Revised 23.10.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 by the American Association for the Study of Liver Diseases. | ||
| 520 | |a BACKGROUND AND AIMS: Immune dysregulation contributes to the pathogenesis of pediatric acute liver failure (PALF). Our aim was to identify immune activation markers (IAMs) in PALF that are associated with a distinct clinical phenotype and outcome | ||
| 520 | |a APPROACH AND RESULTS: Among 47 PALF study participants, 12 IAMs collected ≤6 days after enrollment were measured by flow cytometry and IMMULITE assay on blood natural killer and cluster of differentiation 8-positive (CD8+ ) lymphocytes and subjected to unsupervised hierarchical analyses. A derivation cohort using 4 of 12 IAMs which were available in all participants (percent perforin-positive and percent granzyme-positive CD8 cells, absolute number of CD8 cells, soluble interleukin-2 receptor level) were sufficient to define high (n = 10), medium (n = 15), and low IAM (n = 22) cohorts. High IAM was more frequent among those with indeterminate etiology than those with defined diagnoses (80% versus 20%, P < 0.001). High IAM was associated with higher peak serum total bilirubin levels than low IAM (median peak 21.7 versus 4.8 mg/dL, P < 0.001) and peak coma grades. The 21-day outcomes differed between groups, with liver transplantation more frequent in high IAM participants (62.5%) than those with medium (28.2%) or low IAM (4.8%) (P = 0.002); no deaths were reported. In an independent validation cohort (n = 71) enrolled in a prior study, segregation of IAM groups by etiology, initial biochemistries, and short-term outcomes was similar, although not statistically significant. High serum aminotransferases, total bilirubin levels, and leukopenia at study entry predicted a high immune activation profile | ||
| 520 | |a CONCLUSION: Four circulating T-lymphocyte activation markers identify a subgroup of PALF participants with evidence of immune activation associated with a distinct clinical phenotype and liver transplantation; these biomarkers may identify PALF participants eligible for future clinical trials of early targeted immunosuppression | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 700 | 1 | |a Miethke, Alexander G |e verfasserin |4 aut | |
| 700 | 1 | |a Fei, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Maynor, Sean |e verfasserin |4 aut | |
| 700 | 1 | |a Chapin, Catherine A |e verfasserin |4 aut | |
| 700 | 1 | |a Bleesing, Jacob J H |e verfasserin |4 aut | |
| 700 | 1 | |a Alonso, Estella M |e verfasserin |4 aut | |
| 700 | 1 | |a Squires, Robert H |e verfasserin |4 aut | |
| 700 | 0 | |a Pediatric Acute Liver Failure Study Group |e verfasserin |4 aut | |
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