Differential genetic determination of immune responsiveness to hepatitis B surface antigen and to hepatitis A virus: a vaccination study in twins.
BACKGROUND
The course of viral hepatitis is thought to be affected by genetic host variability and, in particular, by genes of the major histocompatibility locus. Hepatitis A and B vaccination is a useful model to study the effect of host factors on the immune response to viral antigens. We aimed to assess the heritability of the HBsAg (anti-HBs) and anti-hepatitis A virus (anti-HAV) immune response and to estimate the effect of the HLA-DRB1 locus and other genetic loci unlinked to HLA.


METHODS
We did an open prospective study and vaccinated 202 twin pairs with a combined recombinant HBsAg/inactivated hepatitis A vaccine. We measured antibodies to HBsAg and HAV and determined HLA-DRB1* alleles. Heritability was calculated based on variance of antibody response within pairs. Model-fitting analyses were done to analyse genetic and environmental components of vaccine responses.


RESULTS
Anti-HBs and anti-HAV showed heritabilities of 0.61 (95% CI 0.41 to 0.81) and 0.36 (-0.02 to 0.73), respectively. For the anti-HBs immune response, 60% of the phenotypic variance was explained by additive genetic and 40% by non-shared environmental effects. The heritability of the HBsAg vaccine response accounted for by the DRB1* locus was estimated to be 0.25, leaving the remaining heritability of 0.36 to other gene loci.


CONCLUSIONS
Genetic factors have a strong effect on the immune response to HBsAg. Although genes encoded within the MHC are important for this immune response, more than half the heritability is determined outside this complex. Identification of these genes will help us to understand regulation of immune responses to viral proteins.
Höhler
Thomas
T
Department of Internal Medicine, Johannes Gutenberg-University, Mainz, Germany. hoehler@mail.uni-mainz.de
Reuss
Esther
E
Evers
Nina
N
Dietrich
Evi
E
Rittner
Christian
C
Freitag
Christine M
CM
Vollmar
Jens
J
Schneider
Peter M
PM
Fimmers
Rolf
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D035922:Hepatitis A Antibodies / Q000235:genetics; D030041:Hepatitis A virus / Q000276:immunology*; D006510:Hepatitis B Antibodies / Q000097:blood / Q000235:genetics; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology; D006801:Humans; D007110:Immunity, Active / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology; D018433:Twin Studies as Topic; D014611:Vaccination
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D035922:Hepatitis A Antibodies; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D011994:Recombinant Proteins