Digestive Diseases News
Spring/Summer 2008

Research News

Genes Affect Natural Immune Response to Hepatitis C Virus

Genes affecting the activity of natural killer (NK) cells—immune cells that destroy virus-infected cells—vary widely in the population and may explain why some people are more likely to clear the hepatitis C virus (HCV) from their bodies while others are more likely to develop chronic disease.

“There appears to be a certain degree of natural immunity in a small subset of individuals,” Barbara Rehermann, M.D., told attendees of the National Institutes of Health (NIH) Directors’ Seminar entitled “Host Factors Involved in the Control of Hepatitis C Infection.”

Rehermann, who heads the immunology section of the National Institute of Diabetes and Digestive and Kidney Diseases’ (NIDDK) Liver Diseases Branch, cited data from epidemiological genetics studies led by Mary Carrington, Ph.D., at the National Cancer Institute (NCI), which showed an association between recovery from hepatitis C infection and a distinct gene pattern. People who recovered shared similar gene variations affecting the killer cell immunoglobulin-like receptors (KIRs) on NK cells and their ligand human leukocyte antigen (HLA-C), located on target cells. KIR/HLA-C interactions are known to dictate cell targeting by NK cells, but how genetic variations might enhance NK cell activity was unclear.

Sparked by this observation, Rehermann studied the effect of KIR/HLA-C gene combinations on NK cell function in a lab-based virus infection model. Using blood samples from healthy blood donors with defined KIR/HLA-C gene variants, Rehermann determined that when exposed to virus-infected target cells, the immune response of NK cells from individuals with genes for type 1 HLA-C was more rapid and robust than that of NK cells taken from individuals with genes for type 2 HLA-C. Rehermann’s results were published in the March 2008 Journal of Clinical Investigation.

Because NK cells provide a first line of defense against viral pathogens, these results suggest NK cells play a pivotal role during the initial stages of a virus infection.

Crucial Collaboration

Access to a seemingly endless supply of genetically defined cell samples through collaboration with the NCI group was crucial to the study. “I am convinced that this could not have been done at any other place,” said Rehermann. “This is why it is so interesting to be at the NIH.”

About 75 percent of people infected with the hepatitis C virus develop chronic disease, which can lead to cirrhosis of the liver, liver cancer, and liver failure. Hepatitis C affects 500 million people worldwide and is the leading cause of liver transplantation in the United States.

“The projected prevalence of HCV-related liver disease in the United States alone is expected to quadruple within the next 30 years,” said Rehermann. “The future prediction does not look so good,” she added, highlighting the need for better immune modulatory therapies.

The NIDDK’s National Digestive Diseases Information Clearinghouse has more information about hepatitis C at www.digestive.niddk.nih.gov/ddiseases/pubs/hepatitis. To view a videocast of Rehermann’s lecture, visit www.videocast.nih.gov/PastEvents.asp?c=25.

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NIH Publication No. 08–4552
July 2008