Distinct Immune Imprints of Post-Liver Transplantation Hepatitis C Persist Despite Viral Clearance.
Journal
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
ISSN: 1527-6473
Titre abrégé: Liver Transpl
Pays: United States
ID NLM: 100909185
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
21
01
2021
received:
24
09
2020
accepted:
27
01
2021
pubmed:
1
3
2021
medline:
17
6
2021
entrez:
28
2
2021
Statut:
ppublish
Résumé
Recurrence or de novo infection of hepatitis C virus (HCV) after liver transplantation (LT) has been associated with progressive graft hepatitis that can be improved by treatment with novel direct-acting antivirals. Cases of rejection episodes have been described during and after HCV treatment. The evolution of innate and adaptive immune response during and after cure of HCV LT is unknown. We studied 74 protein biomarkers in the plasma of LT patients receiving antiviral therapy. In addition, deep immune phenotyping of both the myeloid and lymphoid immune cell subsets in peripheral blood mononuclear cells was performed. We found that LT patients with active HCV infection displayed distinct alterations of inflammatory protein biomarkers, such as C-X-Cmotif chemokine 10 (CXCL10), caspase 8, C-C motif chemokine 20 (CCL20), CCL19, interferon γ, CUB domain-containing protein 1 (CDCP1), interleukin (IL)-18R1, CXCL11, CCL3, IL8, IL12B, tumor necrosis factor-beta, CXCL6, osteoprotegerin, IL10, fms-related tyrosine kinase 3 ligand, hepatocyte growth factor, urokinase-type plasminogen activator, neurotrophin-3, CCL4, IL6, tumornecrosis factor receptor superfamily member 9, programmed death ligand 1, IL18, and monocyte chemotactic protein 1, and enrichment of peripheral immune cell subsets unlike patients without HCV infection who received transplants. Interestingly, patients who cleared HCV after LT did not normalize the altered inflammatory milieu nor did the peripheral immune cell subsets normalize to what would be seen in the absence of HCV recurrence. Overall, these data indicate that HCV-specific imprints on inflammatory analytes and immune cell subsets after LT are not completely normalized by therapy-induced HCV elimination. This is in line with the clinical observation that cure of HCV after LT did not trigger rejection episodes in many patients.
Identifiants
pubmed: 33641215
doi: 10.1002/lt.26031
pii: 01445473-202106000-00015
doi:
Substances chimiques
Antigens, Neoplasm
0
Antiviral Agents
0
CDCP1 protein, human
0
Cell Adhesion Molecules
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
887-899Subventions
Organisme : centre for research grants SFB900 ''Chronic Infections: Microbial Persistence and its Control''
Organisme : SFB 738 of the German Research Foundation (DFG)
Organisme : Hannover Medical School Transplantation Center
Organisme : German Centre for Infection Research (DZIF)
Organisme : the IFB-Tx (BMBF 01E01302)
Informations de copyright
Copyright © 2021 The Authors. Liver Transplantation published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.
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