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.
| Original language | English |
|---|---|
| Pages (from-to) | 37487-37497 |
| Number of pages | 11 |
| Journal | Oncotarget |
| Volume | 7 |
| Issue number | 25 |
| DOIs | |
| Publication status | Published - 2016 |
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Keywords
- HCC
- HCV
- IL28B
- Immune response
- Immunity
- Immunology and Microbiology Section
- NHL
- TLR2
ASJC Scopus subject areas
- Oncology
Cite this
HCV-related liver and lymphoproliferative diseases : Association with polymorphisms of IL28B and TLR2. / de Re, Valli; De Zorzi, Mariangela; Caggiari, Laura; Lauletta, Gianfranco; Tornesello, Maria Lina; Fognani, Elisa; Miorin, Marta; Racanelli, Vito; Quartuccio, Luca; Gragnani, Laura; Russi, Sabino; Pavone, Fabio; Ghersetti, Michela; Costa, Elena Garlatti; Casarin, Pietro; Bomben, Riccardo; Mazzaro, Cesare; Basaglia, Giancarlo; Berretta, Massimiliano; Vaccher, Emanuela; Izzo, Francesco; Buonaguro, Franco Maria; de Vita, Salvatore; Zignego, Anna Linda; de Paoli, Paolo D.; Dolcetti, Riccardo.
In: Oncotarget, Vol. 7, No. 25, 2016, p. 37487-37497.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - HCV-related liver and lymphoproliferative diseases
T2 - Association with polymorphisms of IL28B and TLR2
AU - de Re, Valli
AU - De Zorzi, Mariangela
AU - Caggiari, Laura
AU - Lauletta, Gianfranco
AU - Tornesello, Maria Lina
AU - Fognani, Elisa
AU - Miorin, Marta
AU - Racanelli, Vito
AU - Quartuccio, Luca
AU - Gragnani, Laura
AU - Russi, Sabino
AU - Pavone, Fabio
AU - Ghersetti, Michela
AU - Costa, Elena Garlatti
AU - Casarin, Pietro
AU - Bomben, Riccardo
AU - Mazzaro, Cesare
AU - Basaglia, Giancarlo
AU - Berretta, Massimiliano
AU - Vaccher, Emanuela
AU - Izzo, Francesco
AU - Buonaguro, Franco Maria
AU - de Vita, Salvatore
AU - Zignego, Anna Linda
AU - de Paoli, Paolo D.
AU - Dolcetti, Riccardo
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - HCC
KW - HCV
KW - IL28B
KW - Immune response
KW - Immunity
KW - Immunology and Microbiology Section
KW - NHL
KW - TLR2
UR - http://www.scopus.com/inward/record.url?scp=84978045031&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84978045031&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.9303
DO - 10.18632/oncotarget.9303
M3 - Article
VL - 7
SP - 37487
EP - 37497
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 25
ER -