Hepatitis C
immunology
Hepatitis C Immunology, Rotterdam Liver Unit
The hepatitis C virus (HCV) is an example of a human viral pathogen that is
difficult to control by the immune system. As a result of this, about 80% of
individuals exposed to HCV become chronically infected. The long-term consequences
of chronic HCV infections can be severe, since patients are at increased risk
for developing liver fibrosis, cirrhosis and/or hepatocellular carcinoma. The
research in our laboratory is aimed at understanding why the immune response
to HCV is insufficient to clear the virus in infected patients, and if the unique
micro-environment of the liver contributes to this. In addition, since current
anti-viral therapy of chronic HCV patients is only partly effective, studies
are being conducted to determine the factors involved in the response to therapy.
This knowledge is important and will be used to improve therapeutic strategies
to treat chronic HCV patients. Our studies combine clinical and fundamental
research.
The fundamental immunological studies are directed by dr. André Boonstra,
while clinical expertise is provided by prof.dr. Harry Janssen and dr. Rob de
Knegt, both experts in the field of viral hepatitis.
Research projects:
- Regulation of HCV-specific T cell responses in chronic HCV patients
- Studies on innate immunity relevant during HCV infection
- The role of intrahepatic immunity in the development of persistence
- Mechanisms of action of current and novel therapies for HCV, and identification
of the factors determining the response to treatment and disease progression
(basic immunological studies, as well as transcriptomics and GWAS)
For further information see also www.hepatitispoli.nl
References by the Boonstra group
2011
- Roomer R, Bergmann JF, Boonstra A, Hansen BE, Haagmans B, Kwadijk-de Gijsel
S, van Vuuren AJ, de Knegt RJ, Janssen HLA.
Continuous interferon alfa-2b infusion in combination with ribavirin for chronic
hepatitis c in treatment experienced patients.
Antiviral Therapy. 2011. Accepted.
- Boonstra A, B-S. Liu, Z.M.A. Groothuismink, J.F. Bergmann, J. de Bruijne,
D.M. Hotho, B. Hansen, A.A. van Vliet, J. van de Wetering, S.P. Fletcher,
L.A. Bauman, M. Rahimy, J.R. Appleman, J.L. Freddo, H.W. Reesink, R.J. de
Knegt, H.L.A. Janssen.
Potent immune activation in chronic hepatitis C patients upon administration
of an oral inducer of endogenous interferons that acts via TLR7.
Antiviral Therapy. 2011. Accepted.
- Bergmann JF, de Bruijne J, Hotho DM, de Knegt RJ, Boonstra A, Weegink CJ,
van Vliet AA, van de Wetering J, Fletcher SP, Bauman LA, Rahimy M, Appleman
JR, Freddo JL, Janssen HL, Reesink HW.
Randomized clinical trial: anti-viral activity of ANA773, an oral inducer
of endogenous interferons acting via TLR7, in chronic HCV.
Alim Pharm Ther. 2011. Accepted.
- Peng C, Liu B-S, de Knegt RJ, Janssen HLA, Boonstra A.
The response to TLR ligation of human CD16+CD14- monocytes is weakly modulated
as a consequence of persistent infection with the hepatitis C virus.
Mol Immunol. 2011.
48: 1505-1511.
- Shi CC, Tjwa ETTL, Biesta PJ, Boonstra A, Xie Q, Janssen HLA, Woltman AM.
Hepatitis B virus suppresses the functional interaction between natural killer
cells and plasmacytoid dendritic cells.
J Vir Hep. 2011. In press.
- Claassen MAA, de Knegt, RJ, Janssen HLA, Boonstra A.
Retention of CD4+CD25+FoxP3+ regulatory T cells in the liver after therapy-induced
hepatitis C virus eradication in humans.
J Virology. 2011.
85(11): 5323-30.
- Liu B-S, Groothuismink ZMA, Janssen HLA, Boonstra A.
Role for IL-10 in inducing functional impairment of monocytes upon TLR4 ligation
in patients with chronic HCV infections.
J
Leukocyte Biol. Jun;89(6):981-8..
- Liu B-S, Janssen HLA, Boonstra A.
IL-29 and IFN? differ in their ability to modulate IL-12 production by TLR-activated
human macrophages, and exhibit differential regulation of the IFN receptor
expression.
Blood. 2011. 117(8):
2385-2395.
- Grotenhuis BA, Franken PF, Swinkels WJC, Boonstra A, van der Valk MA, van
Lanschot JJB, Fodde R.
Early morbidity encountered in the dietary-related mouse model of Barrett's
esophagus: a question of zinc?
Dis Esophagus. 2011.
24: 371-373.
2010
- Arends JE, Claassen MAA, van den Berg CHSB, Nanlohy NM, van Erpecum KJ,
Baak BC, Hoepelman AIM, Boonstra A, van Baarle D.
T-cell responses at baseline and during therapy with peginterferon- and ribavirin
are not associated with outcome in chronic Hepatitis C infected patients.
Antiviral Res. 2010.
87: 353-360.
- Claassen MAA, de Knegt RJ, Turgut D, Tilanus HW, Janssen HLA, Boonstra
A.
Abundant numbers of regulatory T cells localize to the liver of chronic hepatitis
C infected patients and limit the extent of fibrosis.
J Hepatol. 2010.
52: 315-321.
- Woltman AM, Boonstra A, Janssen HLA.
Dendritic cells in chronic viral hepatitis: victims or guardian angels?
Gut. 2010. 59: 115-125.
2009
- Boonstra A, van der Laan LJW, Vanwolleghem T, Janssen HLA.
Experimental models for hepatitis C viral infection.
Hepatology. 2009.
50: 1646-1655.
- Woltman AM, ter Borg MJ, Binda RS, Sprengers D, von Blomberg BME, Scheper
RJ, Hayashi K, Nishi N, Boonstra A, van der Molen R, Janssen HLA.
Alpha-Galactosylceramide in chronic hepatitis B infection: results from a
randomized placebo controlled phase I/II trial.
Antivir Ther. 2009.
14: 809-818
- Liu B, Janssen HLA, Boonstra A.
Modulation of dendritic cell function by persistent viruses.
Review. J Leukoc
Biol. 2009. 85: 205-214.
2008
- Stoop JN, Claassen MAA, Woltman AM, Binda RS, Kuipers EJ, Janssen HLA, van
der Molen RG, Boonstra A.
Intrahepatic regulatory T cells are phenotypically distinct from their peripheral
counterparts in chronic HBV patients, and their frequency depends on the viral
load.
Clin Immunol. 2008.
129: 419-427.
- Boonstra A, Woltman AM, Janssen HLA.
Immunology of hepatitis B and hepatitis C virus infections. Review.
Best Pract Res Clin
Gastroenterol. 2008. 22: 1049-1061.
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