Dynamic Changes of Post-Translationally Modified Forms of CXCL10 and Soluble DPP4 in HCV Subjects Receiving Interferon-Free Therapy
| Autor: | Darragh Duffy, Eric G. Meissner, Henry Masur, Shyam Kottilil, Matthew L. Albert, Jérémie Decalf, Armanda Casrouge |
|---|---|
| Přispěvatelé: | National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Critical Care Medicine Department, National Institutes of Health - NIH, Division of Infectious Diseases, Department of Microbiology and Immunology, Medical University of South Carolina [Charleston] (MUSC), Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Human Virology (IHV), University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System, Centre d'Immunologie Humaine (CIH), This project was supported by federal funds from the intramural program of the National Institute of Allergy and Infectious Diseases, a PasteurInnov grant (Institut Pasteur), and the European Union FP7 grant PoC-HCV (GA n° 601851). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., European Project: 601851,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-2,POC-HCV(2013), Vougny, Marie-Christine, Point-of-care tests to revolutionise the clinical management of patients infected by Hepatitis C virus - POC-HCV - - EC:FP7:HEALTH2013-09-01 - 2016-08-31 - 601851 - VALID, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
MESH: Hepacivirus/drug effects Sofosbuvir MESH: Fluorenes/therapeutic use Hepacivirus lcsh:Medicine MESH: Hepatitis C Chronic/virology Blood plasma medicine.disease_cause Virus Replication chemistry.chemical_compound Recurrence Viral replication MESH: Interferons Enzyme-linked immunoassays MESH: Ribavirin/therapeutic use lcsh:Science MESH: Dipeptidyl Peptidase 4/blood media_common MESH: Treatment Outcome Multidisciplinary biology Hepatitis C virus Convalescence virus diseases MESH: Protein Processing Post-Translational Viral Load MESH: Virus Replication/drug effects 3. Good health Treatment Outcome MESH: Dipeptidyl Peptidase 4/genetics [SDV.IMM]Life Sciences [q-bio]/Immunology Drug Therapy Combination Female Chemokines Viral load medicine.drug Research Article Ledipasvir Adult MESH: Sofosbuvir/therapeutic use MESH: Hepatitis C Chronic/drug therapy [SDV.IMM] Life Sciences [q-bio]/Immunology media_common.quotation_subject Dipeptidyl Peptidase 4 MESH: Chemokine CXCL10/genetics MESH: Convalescence Antiviral Agents MESH: Benzimidazoles/therapeutic use MESH: Viral Load/drug effects Ribavirin MESH: Hepacivirus/physiology medicine Humans Fluorenes MESH: Humans business.industry lcsh:R Correction MESH: Adult Hepatitis C Chronic MESH: Chemokine CXCL10/blood biology.organism_classification Statistical data digestive system diseases MESH: Male Post translational modifications MESH: Recurrence Chemokine CXCL10 Regimen MESH: Drug Therapy Combination chemistry MESH: Hepatitis C Chronic/blood Immunology MESH: Antiviral Agents/therapeutic use lcsh:Q Benzimidazoles Interferons business Protein Processing Post-Translational MESH: Female Biomarkers MESH: Hepatitis C Chronic/genetics |
| Zdroj: | PLoS ONE PLoS ONE, 2015, 10 (7), pp.e0133236. ⟨10.1371/journal.pone.0133236⟩ PLoS ONE, Vol 10, Iss 7, p e0133236 (2015) PLoS ONE, Public Library of Science, 2015, 10 (7), pp.e0133236. ⟨10.1371/journal.pone.0133236⟩ |
| ISSN: | 1932-6203 |
| Popis: | Serum levels of the interferon (IFN)-stimulated chemokine CXCL10 are increased during chronic HCV infection and associate with outcome of IFN-based therapy. Elevated levels of NH2-terminal truncated CXCL10 (3-77aa), produced by DPP4 cleavage, negatively associate with spontaneous clearance of acute HCV infection and sustained virological response (SVR) with IFN-based therapy for chronic infection. The association of different CXCL10 forms and DPP4 with outcome during IFN-free HCV therapy has not been examined. Using novel Simoa assays, plasma was analyzed from HCV genotype-1 (GT1) subjects who relapsed (n = 11) or achieved SVR (n = 10) after sofosbuvir and ribavirin (SOF/RBV) treatment, and from SOF/RBV relapsers who achieved SVR with a subsequent SOF/ledipasvir regimen (n = 9). While the NH2-truncated form of CXCL10 was elevated in HCV infection relative to healthy controls, pre-treatment plasma concentrations of CXCL10 forms failed to stratify subjects based on treatment outcome to IFN-free regimens. However, a trend (statistically non-significant) towards elevated higher levels of total and long CXCL10 was observed pre-treatment in subjects who relapsed. All forms of CXCL10 decreased rapidly following treatment initiation and were again elevated in subjects who experienced HCV relapse, indicating that CXCL10 production may be associated with active viral replication. While soluble DPP4 (sDPP4) and NH2-truncated CXCL10 concentrations were highly correlated, on-treatment sDPP4 levels and activity declined more slowly than CXCL10, suggesting differential regulation. Conclusion These data suggest post-translationally modified forms of CXCL10 will not support the prediction of treatment outcome in HCV GT1 subjects treated with SOF/RBV. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|