Comparison of 125I-interferon-alpha binding to peripheral blood cells from African-Americans and Caucasians with hepatitis C.
Interferon-alpha (IFN-alpha) is the major treatment for chronic hepatitis C virus (HCV) infection. Drug resistance is problematic, particularly among African-Americans who typically show poorer clinical outcomes than Caucasians. The reasons for ethnic variation in IFN-alpha sensitivity are not clear. We speculated that African-American insensitivity to IFN-alpha may be mediated by reduced density of the IFN-alpha receptor (IFN-alphaR) or reduced internalization of the IFN-alpha/IFN-alphaR complex. This speculation was evaluated by comparing binding, uptake and release of 125iodine-labelled IFN-alpha (125I-IFN-alpha) to peripheral blood cells from African-Americans and Caucasians with HCV infection and ethnically matched healthy volunteers. Under various in vitro conditions, binding of 125IFN-alpha to surface receptors was equivalent (P = ns) between African-Americans and Caucasians with HCV infection as well as healthy volunteers (P = ns). Similarly, internalization and release of the 125I-IFN-alpha/IFN-alphaR complex was equivalent (P = ns) between African-Americans and Caucasians with HCV infection and healthy volunteers (P = ns). In addition, ethnicity did not influence (P = ns) IFN-alpha suppression of phytohaemagluttinen induced proliferation. However, IFN-alpha therapy of the same patients showed that African-Americans had lower response rates than Caucasians (14%vs 54%, P < 0.0001). In summary, IFN-alpha resistance among African-Americans is not mediated by intrinsic differences in IFN-alpha receptor density or internalization.
Kimball
P
P
Departments of Surgery and Gastroenterology, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, VA 23298, USA. pkimball@gems.vcu.edu
Verbeke
S
S
Shiffman
M
M
D044383:Black People; D002478:Cells, Cultured; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000208:ethnology / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism* / Q000627:therapeutic use; D007457:Iodine Radioisotopes; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism; D044465:White People; D001741:Black or African American
D016898:Interferon-alpha; D007457:Iodine Radioisotopes; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta