Apolipoprotein H expression is associated with IL28B genotype and viral clearance in hepatitis C virus infection

Autor: Vincent Mallet, Christophe Hézode, Rasha Mamdouh, Mona Rafik, Alexandre Soulier, Isabelle Rosa, Amira Mohsen, Mai El-Daly, Lenaig Le-Fouler, Philippe Renard, Jacques Izopet, Philippe Bonnard, Melissa E. Laird, Armanda Casrouge, Arnaud Fontanet, Stanislas Pol, Mostafa K. Mohamed, Darragh Duffy, Jean-Michel Pawlotsky, Matthew L. Albert, Mohamed Abdel-Hamid
Přispěvatelé: Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Community Medicine Department, National Research Center, Faculty of medicine, Université Ain Shams, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), liver diseases research unit, National Hepatology & Tropical Medicine Research Institute, Minia University, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CNR for Viral Hepatitis B, C, and D, Hôpital Henri Mondor, Service d'hépato-gastro-entérologie [APHP Henri Mondor], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of gastroenterology and hepatology, Hôpital Victor Dupouy, Service des maladies infectieuses et tropicales [CHU Tenon], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Virologie, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by ANRS grants 12210, 12199, 12135 (MLA, AF), the European Research Council Young Investigator Award (MLA), and the European FP7 project SPHINX (ID 261365). Chronic HCV patient samples were provided from an Inserm sponsored clinical trial and also from the control arm of the REALIZE trial as run by Tibotec (Trial N° VX-950-TiDP24-C216). HCV/HIV patient samples were provided as part of the ANRS HC 20 ETOC study (NCT00901524)., European Project: 261365,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,SPHINX(2010), Epidémiologie des Maladies Emergentes, Pasteur-Cnam risques infectieux et émergents (PACRI), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
Very low-density lipoprotein
MESH: Ribavirin/administration & dosage
Apolipoprotein B
MESH: HIV Infections*/complications
IL28B
HIV Infections
Hepacivirus
Virus Replication
medicine.disease_cause
Polyethylene Glycols
chemistry.chemical_compound
MESH: Hepacivirus*/drug effects
Host factor
MESH: Treatment Outcome
MESH: Aged
MESH: Middle Aged
biology
Coinfection
Hepatitis C virus
MESH: Polymorphism
Single Nucleotide
Middle Aged
Viral Load
MESH: Hepatitis C*/complications Hepatitis
MESH: Virus Replication/drug effects
Hepatitis C
3. Good health
Treatment Outcome
beta 2-Glycoprotein I
MESH: Interferon-alpha/administration & dosage
MESH: beta 2-Glycoprotein I*/blood
MESH: Antiviral Agents/administration & dosage
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
MESH: Viral Load
Apolipoprotein H
Adult
Quantitative trait loci
MESH: C*/drug therapy Hepatitis
MESH: beta 2-Glycoprotein I*/genetic
Single-nucleotide polymorphism
Antiviral Agents
Polymorphism
Single Nucleotide
Ribavirin
MESH: Interleukins/genetics
medicine
Humans
SNP
Aged
MESH: C*/immunology Hepatitis
MESH: HIV Infections*/drug therapy
Hepatology
Interleukins
MESH: C*/physiopathology Humans
Interferon-alpha
MESH: Polyethylene Glycols/administration & dosage
MESH: Adult
Virology
MESH: Male
MESH: HIV Infections*/immunology
MESH: Coinfection
MESH: Hepacivirus*/physiology
Lipid metabolism
Apolipoproteins
chemistry
Immunology
biology.protein
MESH: C*/genetics Hepatitis
Interferons
MESH: Female
Zdroj: Journal of Hepatology
Journal of Hepatology, Elsevier, 2014, 61 (4), pp.770-776. ⟨10.1016/j.jhep.2014.05.040⟩
Journal of Hepatology; Vol 61
Journal of Hepatology, 2014, 61 (4), pp.770-776. ⟨10.1016/j.jhep.2014.05.040⟩
ISSN: 0168-8278
1600-0641
DOI: 10.1016/j.jhep.2014.05.040⟩
Popis: International audience; BACKGROUND & AIMS:HCV requires host lipid metabolism for replication, and apolipoproteins have been implicated in the response to treatment.METHODS:We examined plasma apolipoprotein concentrations in three cohorts of patients: mono-infected patients with symptomatic acute hepatitis C (aHCV); those undergoing treatment for chronic hepatitis C (cHCV); and HIV/HCV co-infected patients being treated for their chronic hepatitis C. We also evaluated associations between apolipoproteins and IL28B polymorphisms, a defined genetic determinant of viral clearance.RESULTS:Plasma apolipoprotein H (ApoH) levels were significantly higher in patients who achieved spontaneous clearance or responded to pegylated-interferon/ribavirin therapy. Strikingly, patients carrying the IL28B rs12979860 CC SNP correlated with the plasma concentration of ApoH in all three cohorts. Both ApoH and IL28B CC SNP were associated with HCV clearance in univariate analysis. Additional multivariate analysis revealed that the association between IL28B and HCV clearance was closely linked to that of Apo H and HCV clearance, suggesting that both belong to the same biological pathway to clearance. The association between IL28B CC SNP and ApoH was not observed in healthy individuals, suggesting that early post-infection events trigger differential ApoH expression in an IL28B allele dependent manner.CONCLUSIONS:This relationship identifies ApoH as the first induced protein quantitative trait associated with IL28B, and characterises a novel host factor implicated in HCV clearance
Databáze: OpenAIRE
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