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Correlation of Immune Markers With Outcomes in Biliary Atresia Following Intravenous Immunoglobulin Therapy
Biliary atresia is a progressive fibroinflammatory cholangiopathy of infancy that is associated with activation of innate and adaptive immune responses targeting bile ducts. A recently completed multicenter phase I/IIA trial of intravenous immunoglobulin in biliary atresia did not improve serum tota...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492477/ https://www.ncbi.nlm.nih.gov/pubmed/31061956 http://dx.doi.org/10.1002/hep4.1332 |
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author | Kim, Sehee Moore, Jeffrey Alonso, Estella Bednarek, Joseph Bezerra, Jorge A. Goodhue, Catherine Karpen, Saul J. Loomes, Kathleen M. Magee, John C. Ng, Vicky L. Sherker, Averell H. Smith, Caroline Spino, Cathie Venkat, Veena Wang, Kasper Sokol, Ronald J. Mack, Cara L. |
author_facet | Kim, Sehee Moore, Jeffrey Alonso, Estella Bednarek, Joseph Bezerra, Jorge A. Goodhue, Catherine Karpen, Saul J. Loomes, Kathleen M. Magee, John C. Ng, Vicky L. Sherker, Averell H. Smith, Caroline Spino, Cathie Venkat, Veena Wang, Kasper Sokol, Ronald J. Mack, Cara L. |
author_sort | Kim, Sehee |
collection | PubMed |
description | Biliary atresia is a progressive fibroinflammatory cholangiopathy of infancy that is associated with activation of innate and adaptive immune responses targeting bile ducts. A recently completed multicenter phase I/IIA trial of intravenous immunoglobulin in biliary atresia did not improve serum total bilirubin levels at 90 days after hepatoportoenterostomy or survival with the native liver at 1 year. A mechanistic aim of this trial was to determine if the peripheral blood immunophenotype was associated with clinical outcomes. Flow cytometry of peripheral blood cell markers (natural killer [NK], macrophage subsets, T‐ and B‐cell subsets, regulatory T cells), neutrophils, and activation markers (clusters of differentiation [CD]38, CD69, CD86, human leukocyte antigen‐DR isotype [HLA‐DR]) was performed on 29 patients with biliary atresia at baseline and at 60, 90, 180, and 360 days after hepatoportoenterostomy. Plasma cytokines and neutrophil products were also measured. Spearman correlations of change of an immune marker from baseline to day 90 with change in serum bilirubin revealed that an increase in total bilirubin correlated with 1) increased percentage of HLA‐DR(+)CD38(+) NK cells and expression of NK cell activation markers CD69 and HLA‐DR, 2) decreased percentage of regulatory T cells, and 3) increased interleukin (IL)‐8 and associated neutrophil products (elastase and neutrophil extracellular traps). Cox modeling revealed that the change from baseline to day 60 of the percentage of HLA‐DR(+)CD38(+) NK cells and plasma IL‐8 levels was associated with an increased risk of transplant or death by day 360. Conclusion: Poor outcomes in biliary atresia correlated with higher peripheral blood NK cells and IL‐8 and lower regulatory T cells. Future studies should include immunotherapies targeting these pathways in order to protect the biliary tree from ongoing damage. |
format | Online Article Text |
id | pubmed-6492477 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64924772019-05-06 Correlation of Immune Markers With Outcomes in Biliary Atresia Following Intravenous Immunoglobulin Therapy Kim, Sehee Moore, Jeffrey Alonso, Estella Bednarek, Joseph Bezerra, Jorge A. Goodhue, Catherine Karpen, Saul J. Loomes, Kathleen M. Magee, John C. Ng, Vicky L. Sherker, Averell H. Smith, Caroline Spino, Cathie Venkat, Veena Wang, Kasper Sokol, Ronald J. Mack, Cara L. Hepatol Commun Original Articles Biliary atresia is a progressive fibroinflammatory cholangiopathy of infancy that is associated with activation of innate and adaptive immune responses targeting bile ducts. A recently completed multicenter phase I/IIA trial of intravenous immunoglobulin in biliary atresia did not improve serum total bilirubin levels at 90 days after hepatoportoenterostomy or survival with the native liver at 1 year. A mechanistic aim of this trial was to determine if the peripheral blood immunophenotype was associated with clinical outcomes. Flow cytometry of peripheral blood cell markers (natural killer [NK], macrophage subsets, T‐ and B‐cell subsets, regulatory T cells), neutrophils, and activation markers (clusters of differentiation [CD]38, CD69, CD86, human leukocyte antigen‐DR isotype [HLA‐DR]) was performed on 29 patients with biliary atresia at baseline and at 60, 90, 180, and 360 days after hepatoportoenterostomy. Plasma cytokines and neutrophil products were also measured. Spearman correlations of change of an immune marker from baseline to day 90 with change in serum bilirubin revealed that an increase in total bilirubin correlated with 1) increased percentage of HLA‐DR(+)CD38(+) NK cells and expression of NK cell activation markers CD69 and HLA‐DR, 2) decreased percentage of regulatory T cells, and 3) increased interleukin (IL)‐8 and associated neutrophil products (elastase and neutrophil extracellular traps). Cox modeling revealed that the change from baseline to day 60 of the percentage of HLA‐DR(+)CD38(+) NK cells and plasma IL‐8 levels was associated with an increased risk of transplant or death by day 360. Conclusion: Poor outcomes in biliary atresia correlated with higher peripheral blood NK cells and IL‐8 and lower regulatory T cells. Future studies should include immunotherapies targeting these pathways in order to protect the biliary tree from ongoing damage. John Wiley and Sons Inc. 2019-03-25 /pmc/articles/PMC6492477/ /pubmed/31061956 http://dx.doi.org/10.1002/hep4.1332 Text en © 2019 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Kim, Sehee Moore, Jeffrey Alonso, Estella Bednarek, Joseph Bezerra, Jorge A. Goodhue, Catherine Karpen, Saul J. Loomes, Kathleen M. Magee, John C. Ng, Vicky L. Sherker, Averell H. Smith, Caroline Spino, Cathie Venkat, Veena Wang, Kasper Sokol, Ronald J. Mack, Cara L. Correlation of Immune Markers With Outcomes in Biliary Atresia Following Intravenous Immunoglobulin Therapy |
title | Correlation of Immune Markers With Outcomes in Biliary Atresia Following Intravenous Immunoglobulin Therapy |
title_full | Correlation of Immune Markers With Outcomes in Biliary Atresia Following Intravenous Immunoglobulin Therapy |
title_fullStr | Correlation of Immune Markers With Outcomes in Biliary Atresia Following Intravenous Immunoglobulin Therapy |
title_full_unstemmed | Correlation of Immune Markers With Outcomes in Biliary Atresia Following Intravenous Immunoglobulin Therapy |
title_short | Correlation of Immune Markers With Outcomes in Biliary Atresia Following Intravenous Immunoglobulin Therapy |
title_sort | correlation of immune markers with outcomes in biliary atresia following intravenous immunoglobulin therapy |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492477/ https://www.ncbi.nlm.nih.gov/pubmed/31061956 http://dx.doi.org/10.1002/hep4.1332 |
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