Hepatitis B infection

Researchers involved
A.M. Woltman (Andrea), PhD Group leader [CV]	Dr A. van Montfoort (Nadine), Phd	A. Boltjes (Arjan), MSc, Phd student	L. van de Laar (Lianne), MSc, PhD student
E.T.T.L. Tjwa (Eric), MD, PhD student	C. Shi (Sophie), MSc, Phd student	P. Biesta (Paula), BSc, technician	A. van den bosch (Aniek), BSc, technician
G. van Oord (Gertine), Bsc, Technician	Prof H.L.A. Janssen (Harry), MD,PhD [CV]

Hepatitis B immunology
Worldwide over 350 million people are chronically infected with hepatitis B virus (HBV) due to an inadequate immune response towards the virus. Due to lack of an effective therapy, each year about 1 million people die due to HBV-related liver failure and hepatocellular carcinoma. The development of an effective anti-HBV therapy requires insight in the mechanisms underlying anti-viral immunity, HBV persistence and non-response to therapy.





Innate immunity
In sharp contrast to other viruses, HBV infection does not induce a strong innate immune response. Macrophages, natural killer (NK) cells, both found in the liver at unique high frequencies, and dendritic cells (DC) are potent innate immune cells with anti-viral and immune regulatory properties. These cells of the innate immune system not only serve as first-line defense against viruses, but also regulate the quality of virus-specific T and B cell responses.

Research projects:
- The function of DC and NK cells in HBV infected patients (liver and blood)
- The effect of HBV on the function of antigen presenting cells and NK cells and the consequences for the regulation of HBV-specific immunity
- Molecular mechanisms regulating human DC development and function
- Mechanisms of action of current and novel therapies for chronic hepatitis B
- Identification of genetic and immunological factors determining disease outcome and response to treatment

Our studies combine clinical and fundamental research. The fundamental immunological studies are directed by dr. Andrea Woltman, while clinical expertise is provided by prof.dr. Harry Janssen. For further information see also www.hepatitispoli.nl

Selected Publications

• Tjwa ETTL, Van Oord GW, Hegmans JP, Janssen HLA, Woltman AM.
  Viral load reduction improves activation and function of natural killer cells in patients with chronic hepatitis B.
  J. Hepatol. In press

• Van de Laar L, Buitenhuis M, Wensveen FM, Janssen HLA, Coffer PJ, Woltman AM.
  Human CD34-derived myeloid dendritic cell development requires intact PI3K-PKB-mTOR signaling.
  J. Immunol. 184:6600-6611, 2010

• Woltman AM, Boonstra A, Janssen HLA.
  Dendritic cells in viral hepatitis: victims or guardian angels?
  Gut 59(1):115-25, 2010
• Stoop JN, Woltman AM, Biesta PJ, Kusters JG, Kuipers EJ, Janssen HLA, van der Molen RG.
  Tumor necrosis factor- inhibits the suppressive effect of regulatory T cells on the HBV-specific immune response.
  Hepatology 46:699-705, 2007.

• Woltman AM, van der Kooij SW, Coffer PJ, Offringa R, Daha MR, van Kooten C.
  Rapamycin specifically interferes with GM-CSF signaling in human dendritic cells leading to apoptosis via increased p27KIP1 expression.
  Blood 101:1439-1445, 2003.
  

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