Journal
HUMAN IMMUNOLOGY
Volume 69, Issue 3, Pages 158-164Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.humimm.2008.01.019
Keywords
immunoglobulin; GM and KM allotypes; IgG antibodies; proteins E1 and E2; hepatitis C virus; humoral immunity
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Funding
- NHGRI NIH HHS [HG003054] Funding Source: Medline
- NIDA NIH HHS [DA012568, R01 DA012568, DA13324, R01 DA013324, R56 DA012568] Funding Source: Medline
- NIDDK NIH HHS [DK068555, DK070877, R21 DK068555, R01 DK070877-03, R01 DK070877] Funding Source: Medline
- NIGMS NIH HHS [R01 GM028356, GM28356, R37 GM028356] Funding Source: Medline
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Immunoglobulin (lg) GM and KM allotypes-genetic markers of gamma and K chains, respectively-are associated with the outcome of hepatitis C virus (HCV) infection, but the underlying mechanisms are not well understood. We hypothesized that GM and KM allotypes could contribute to the outcome of HCV infection by influencing the levels of IgG antibodies to the HCV glycoproteins E1E2. We serologically allotyped 100 African American individuals with persistent HCV infection for GM and KM markers and measured anti-E1E2 antibodies. Subjects with the GM 1,17 5,13 phenotype had significantly higher levels of anti-E1E2 antibodies than subjects who tacked this phenotype (p = 0.008). Likewise, subjects with the KM 1-carrying phenotypes had higher levels of anti-E1E2 antibodies than subjects who lacked these phenotypes (p = 0.041). Median titers were fourfold higher in persons expressing both GM 1,17 5,13 and KM 1-carrying phenotypes compared with those who tacked these phenotypes (p = 0.011). Interactive effects of these GM-KM phenotypes were previously found to be highly significantly associated with spontaneous HCV clearance. Results presented here show that lg allotypes contribute to the interindividual differences in humoral immunity to the HCV epitopes, a finding that may provide a mechanistic explanation for their involvement in the outcome of HCV infection. (c) 2008 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
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