title: HCV-related liver and lymphoproliferative diseases: association with polymorphisms of IL28B and TLR2.
abstract: To explore the relationship between innate immunity and hepatitis C Virus (HCV) in determining the risk of cirrhosis (CIR), hepatocellular carcinoma (HCC), mixed cryoglobulinemia syndrome (MCS) and non-Hodgkin lymphoma (NHL), we investigated the impact of the toll-like receptor-2 (TLR2) and interleukin-28B (IL28B) genetic variants. TLR2 -174 del variant was associated with TLR2 expression and with specific downstream molecules that drive the expression of different interleukins; rs12979860 Il28B was important in response to interferon-treatment and in spontaneous clearance of HCV. The risk for liver and lymphoproliferative diseases in HCV progression was clarified by stratifying 862 HCV-positive patients into groups based on liver (CIR, HCC) and lymphoproliferative HCV-related diseases (MCS, NHL) and compared with chronic HCV (CHC) infection. Analysis of TLR2-IL28B haplotypes showed an association of wild type haplotype with the lymphoproliferative diseases (OR 1.77, p = 0.029) and a slight increase in HCV viral load (HR 1.38, p = 0.054). Wild type haplotype (TLR2 ins/ins- IL28B C/C) was also found associated with older age in patients with an hepatic diseases (in CIR and in HCC p = 0.038 and p = 0.020, respectively) supporting an effect of innate immunity in the liver disease progression. TLR2 and IL28B polymorphisms in combination showed a role in the control of HCV viral load and different HCV disease progression.
authors.affiliation: Bio-Proteomics Facility/ Cancer Bioimmunotherapy, Department of Translational Research, Centro di Riferimento Oncologico (CRO), National Cancer Institute, Aviano, Italy.
authors.forename: Valli
authors.initials: V
authors.lastname: De Re
authors.affiliation: Bio-Proteomics Facility/ Cancer Bioimmunotherapy, Department of Translational Research, Centro di Riferimento Oncologico (CRO), National Cancer Institute, Aviano, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: De Zorzi
authors.affiliation: Bio-Proteomics Facility/ Cancer Bioimmunotherapy, Department of Translational Research, Centro di Riferimento Oncologico (CRO), National Cancer Institute, Aviano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Caggiari
authors.affiliation: Liver Unit, Division of Internal Medicine and Clinical Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Lauletta
authors.affiliation: Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori "Fondazione G. Pascale" - IRCCS, Napoli, Italy.
authors.forename: Maria Lina
authors.initials: ML
authors.lastname: Tornesello
authors.affiliation: Interdepartmental Center for Systemic Manifestations of Hepatitis Virus MASVE, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Fognani
authors.affiliation: Cytogenetics and Molecular Biology Unit, Santa Maria degli Angeli Hospital Pordenone, Pordenone, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Miorin
authors.affiliation: Immunology Section, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Racanelli
authors.affiliation: Clinic of Rheumatology, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Quartuccio
authors.affiliation: Interdepartmental Center for Systemic Manifestations of Hepatitis Virus MASVE, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Gragnani
authors.affiliation: Liver Unit, Division of Internal Medicine and Clinical Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Sabino
authors.initials: S
authors.lastname: Russi
authors.affiliation: Liver Unit, Division of Internal Medicine and Clinical Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pavone
authors.affiliation: Internal Medicine-Liver Unit, Santa Maria degli Angeli Hospital Pordenone, Pordenone, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Ghersetti
authors.affiliation: Internal Medicine-Liver Unit, Santa Maria degli Angeli Hospital Pordenone, Pordenone, Italy.
authors.forename: Elena Garlatti
authors.initials: EG
authors.lastname: Costa
authors.affiliation: Internal Medicine-Liver Unit, Santa Maria degli Angeli Hospital Pordenone, Pordenone, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Casarin
authors.affiliation: Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico (CRO), National Cancer Institute, Aviano, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bomben
authors.affiliation: Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico (CRO), National Cancer Institute, Aviano, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Mazzaro
authors.affiliation: Microbiology-Immunology and Virology Unit, Centro di Riferimento Oncologico (CRO), National Cancer Institute, Aviano, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Basaglia
authors.affiliation: Medical Oncology, Centro di Riferimento Oncologico (CRO), National Cancer Institute, Aviano, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Berretta
authors.affiliation: Medical Oncology, Centro di Riferimento Oncologico (CRO), National Cancer Institute, Aviano, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Vaccher
authors.affiliation: Hepatobiliary Unit, Istituto Nazionale Tumori "Fondazione G. Pascale" - IRCCS, Napoli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Izzo
authors.affiliation: Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori "Fondazione G. Pascale" - IRCCS, Napoli, Italy.
authors.forename: Franco Maria
authors.initials: FM
authors.lastname: Buonaguro
authors.affiliation: Clinic of Rheumatology, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Vita
authors.affiliation: Interdepartmental Center for Systemic Manifestations of Hepatitis Virus MASVE, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Anna Linda
authors.initials: AL
authors.lastname: Zignego
authors.affiliation: Scientific Directorate, Centro di Riferimento Oncologico (CRO), National Cancer Institute, Aviano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: De Paoli
authors.affiliation: Cancer Bio-Immunotherapy, Department of Translational Research, Centro di Riferimento Oncologico (CRO), National Cancer Institute, Aviano, Italy.|University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Dolcetti
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000473:pathology / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; D051195:Toll-Like Receptor 2; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C495342:TLR2 protein, human
keywords: HCC; HCV; IL28B; Immune response; Immunity; Immunology and Microbiology Section; NHL; TLR2