Effector memory CD8 T-cells as a novel peripheral blood biomarker for activated T-cell pediatric acute liver failure.
A distinct phenotype of pediatric acute liver failure (PALF) has been identified, labeled activated T-cell hepatitis. These patients, previously included within the indeterminate group, have evidence of systemic immune activation and liver biopsy specimens with dense infiltration of CD8+ T-cells. We...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0286394 |
| _version_ | 1797799845316001792 |
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| author | Catherine A Chapin Thomas M Burn Tamir Diamond Kathleen M Loomes Estella M Alonso Edward M Behrens |
| author_facet | Catherine A Chapin Thomas M Burn Tamir Diamond Kathleen M Loomes Estella M Alonso Edward M Behrens |
| author_sort | Catherine A Chapin |
| collection | DOAJ |
| description | A distinct phenotype of pediatric acute liver failure (PALF) has been identified, labeled activated T-cell hepatitis. These patients, previously included within the indeterminate group, have evidence of systemic immune activation and liver biopsy specimens with dense infiltration of CD8+ T-cells. We aimed to evaluate the peripheral blood T-cell phenotype in PALF patients with activated T-cell hepatitis compared to indeterminate cause. PALF patients with unknown etiology age 1-17 years were prospectively enrolled between 2017-2020. Within the unknown group, patients were classified as either activated T-cell hepatitis if they had a liver biopsy with dense or moderate CD8 staining and an elevated soluble interleukin-2 receptor level, or they were classified as indeterminate if they did not meet these criteria. Whole blood was collected for flow cytometry and T-cell phenotyping. Four patients with activated T-cell hepatitis and 4 patients with indeterminate PALF were enrolled. Activated T-cell hepatitis patients had significantly greater percentage of CD8 T-cells that were effector memory (TEM) phenotype compared to indeterminate PALF patients (median 66.8% (IQR 57.4-68.7) vs 19.1% (IQR 13.4-25.2), P = 0.03). In addition, CD8+ TEM cells in activated T-cell hepatitis patients were significantly more likely to be CD103 positive, a marker of tissue resident memory T-cells, compared to indeterminate PALF patients (median 12.4% (IQR 9.5-14.7) vs 4.7% (IQR 4.5-5.3), P = 0.03). We found patients with activated T-cell hepatitis can be identified by the unique pattern of increased percentage of peripheral blood effector memory CD8+ CD103+ T-cells. These findings will guide future studies exploring the T-cell phenotype for these patients and whether they may respond to directed immunosuppressive therapies. |
| first_indexed | 2024-03-13T04:26:05Z |
| format | Article |
| id | doaj.art-9d4b7210c09a457e93765223814102db |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-13T04:26:05Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9d4b7210c09a457e93765223814102db2023-06-20T05:31:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01186e028639410.1371/journal.pone.0286394Effector memory CD8 T-cells as a novel peripheral blood biomarker for activated T-cell pediatric acute liver failure.Catherine A ChapinThomas M BurnTamir DiamondKathleen M LoomesEstella M AlonsoEdward M BehrensA distinct phenotype of pediatric acute liver failure (PALF) has been identified, labeled activated T-cell hepatitis. These patients, previously included within the indeterminate group, have evidence of systemic immune activation and liver biopsy specimens with dense infiltration of CD8+ T-cells. We aimed to evaluate the peripheral blood T-cell phenotype in PALF patients with activated T-cell hepatitis compared to indeterminate cause. PALF patients with unknown etiology age 1-17 years were prospectively enrolled between 2017-2020. Within the unknown group, patients were classified as either activated T-cell hepatitis if they had a liver biopsy with dense or moderate CD8 staining and an elevated soluble interleukin-2 receptor level, or they were classified as indeterminate if they did not meet these criteria. Whole blood was collected for flow cytometry and T-cell phenotyping. Four patients with activated T-cell hepatitis and 4 patients with indeterminate PALF were enrolled. Activated T-cell hepatitis patients had significantly greater percentage of CD8 T-cells that were effector memory (TEM) phenotype compared to indeterminate PALF patients (median 66.8% (IQR 57.4-68.7) vs 19.1% (IQR 13.4-25.2), P = 0.03). In addition, CD8+ TEM cells in activated T-cell hepatitis patients were significantly more likely to be CD103 positive, a marker of tissue resident memory T-cells, compared to indeterminate PALF patients (median 12.4% (IQR 9.5-14.7) vs 4.7% (IQR 4.5-5.3), P = 0.03). We found patients with activated T-cell hepatitis can be identified by the unique pattern of increased percentage of peripheral blood effector memory CD8+ CD103+ T-cells. These findings will guide future studies exploring the T-cell phenotype for these patients and whether they may respond to directed immunosuppressive therapies.https://doi.org/10.1371/journal.pone.0286394 |
| spellingShingle | Catherine A Chapin Thomas M Burn Tamir Diamond Kathleen M Loomes Estella M Alonso Edward M Behrens Effector memory CD8 T-cells as a novel peripheral blood biomarker for activated T-cell pediatric acute liver failure. PLoS ONE |
| title | Effector memory CD8 T-cells as a novel peripheral blood biomarker for activated T-cell pediatric acute liver failure. |
| title_full | Effector memory CD8 T-cells as a novel peripheral blood biomarker for activated T-cell pediatric acute liver failure. |
| title_fullStr | Effector memory CD8 T-cells as a novel peripheral blood biomarker for activated T-cell pediatric acute liver failure. |
| title_full_unstemmed | Effector memory CD8 T-cells as a novel peripheral blood biomarker for activated T-cell pediatric acute liver failure. |
| title_short | Effector memory CD8 T-cells as a novel peripheral blood biomarker for activated T-cell pediatric acute liver failure. |
| title_sort | effector memory cd8 t cells as a novel peripheral blood biomarker for activated t cell pediatric acute liver failure |
| url | https://doi.org/10.1371/journal.pone.0286394 |
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