Four Biomarkers Linked to Activation of Cluster of Differentiation 8–Positive Lymphocytes Predict Clinical Outcomes in Pediatric Acute Liver Failure
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...
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| Vydáno v: | Hepatology (Baltimore, Md.) Ročník 73; číslo 1; s. 233 - 246 |
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| Hlavní autoři: | , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
01.01.2021
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| ISSN: | 0270-9139, 1527-3350, 1527-3350 |
| On-line přístup: | Získat plný text |
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| Shrnutí: | 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. |
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| Bibliografie: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 These authors contributed equally to this work. Author Contributions: M.L. was responsible for study concept and design, data acquisition, data analysis and interpretation, drafting the manuscript, and critical revision. A. M. was responsible for study concept and design, analysis and interpretation, drafting the manuscript, and critical revision. L.F. was responsible for study concept and design, analysis and interpretation, drafting the manuscript, critical revision, and statistical analysis. S.M. was responsible for analysis and interpretation, critical revision, and statistical analysis. C.C. was responsible for analysis and interpretation and critical revision. J.B. was responsible for analysis and interpretation and critical revision. E.A. was responsible for analysis and interpretation and critical revision. R.S. was responsible for study concept and design, data acquisition, analysis and interpretation, drafting the manuscript, critical revision, obtaining funding, and administration. |
| ISSN: | 0270-9139 1527-3350 1527-3350 |
| DOI: | 10.1002/hep.31271 |