Premium
Comparison of 125 I‐interferon‐ α binding to peripheral blood cells from African–Americans and Caucasians with hepatitis C
Author(s) -
Kimball P.,
Verbeke S.,
Shiffman M.
Publication year - 2003
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1046/j.1365-2893.2003.00444.x
Subject(s) - alpha interferon , internalization , alpha (finance) , medicine , immunology , hepatitis c , hepatitis c virus , interferon , receptor , hepatitis b virus , virology , virus , surgery , construct validity , patient satisfaction
Summary. Interferon‐ α (IFN‐ α ) 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‐ α sensitivity are not clear. We speculated that African–American insensitivity to IFN‐ α may be mediated by reduced density of the IFN‐ α receptor (IFN‐ α R) or reduced internalization of the IFN‐ α /IFN‐ α R complex. This speculation was evaluated by comparing binding, uptake and release of 125 iodine‐labelled IFN‐ α ( 125 I‐IFN‐ α ) to peripheral blood cells from African–Americans and Caucasians with HCV infection and ethnically matched healthy volunteers. Under various in vitro conditions, binding of 125 IFN‐ α 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 125 I‐IFN‐ α /IFN‐ α R 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‐ α suppression of phytohaemagluttinen induced proliferation. However, IFN‐ α therapy of the same patients showed that African–Americans had lower response rates than Caucasians (14% vs 54%, P < 0.0001). In summary, IFN‐ α resistance among African–Americans is not mediated by intrinsic differences in IFN‐ α receptor density or internalization.