HBeAg
Seroconversion Is Associated with HBV-specific T-cell Activity in Children with
Hepatitis B
A
majority of adults infected with hepatitis B virus
(HBV) clear the virus without treatment, but children infected perinatally
or early in life are more likely to develop chronic infection.
As
reported at the 57th annual meeting of the American Association for Liver Diseases
(AASLD) last month in Boston, researchers at King's College London School of Medicine
explored factors associated with HBV "e" antigen (HBeAg) clearance in
pediatric patients.
"HBV
starts to be recognized by the immune system in adulthood with consequent HBeAg
seroconversion," they wrote. "Mutations within HBV pre-core and core
regions are usually present in HBeAg negative chronic hepatitis B patients. Vigorous
and broad HBV-specific immune reactivity is associated with successful control
of viral replication. The selective pressure of immune system could be responsible
for the development of mutations, which may interfere with efficient immune control
of the virus."
The
investigators conducted a study to assess T-helper 1 (Th1), Th2, and cytotoxic
T-lymphocytes HBV-specific immune reactivity in relation to point mutations within
HBV pre-core and core promoter regions and amino acid substitutions in HBV core
immunodominant epitopes in 40 children (median age 11.8 years) infected with HBV
during infancy; 27 HBeAg positive and 13 HBeAg negative children were studied.
The number of
HBV-specific CD4+ peripheral blood mononuclear cells (PBMCs) producing interferon-gamma
and interleukin-4 (IL-4) upon stimulation with HBV recombinant antigens (HBcAg,
HBeAg, and HBsAg) was evaluated by Elispot assay. In 20 HLA-A2+ subjects, CD8+
reactivity was determined by interferon-gamma Elispot. Point mutations within
HBV pre-core and core promoter regions and amino acid substitutions in HBV-core
gene immunodominant epitopes were analyzed in HBV DNA extracted from patients'
serum.
Results
•
Frequency
of HBeAg-specific CD4+ cells producing interferon-gamma was higher in HBeAg negative
than in HBeAg positive children (P = 0.034).
•
While
Th1 CD4+ reactivity to HBcAg and HBsAg and CD8+ reactivity to HBV-core 18-27 peptide
were similar in the 2 groups, the proportion of HBV-specific CD4+ cells producing
IL-4 tended to be higher in HBeAg positive patients than in HBeAg negative subjects
(P = 0.143).
•
Point
mutations within HBV pre-core and core promoter regions and amino acid substitutions
in immunodominant epitopes of the HBV-core gene were more frequent in HBeAg negative
than HBeAg positive patients (pre-core 4.8 vs 2.5, P = 0.001; core 6.6 vs 5.2,
P = 0.029).
Conclusion
"Clearance
of HBeAg in children is associated with HBV-specific Th1 immune reactivity and
higher numbers of mutations, especially in HBV pre-core region," the investigators
concluded. "These findings suggest that HBV-specific T-cell responses are
involved in control of virus (HBeAg clearance), but paradoxically they are responsible
for the emergence of mutations within HBV pre-core and core regions possibly as
the result of their immunoselective pressure."
The
researchers also presented
a second report describing the association between HBeAg clearance and a high
number of mutations within the pre-core and core regions of HBV. [LINK: http://www.hivandhepatitis.com/2006icr/aasld/docs/111706_e.html]
11/21/06
Reference I
Carey, A Giannattasio, S Bansal, and others. HBeAg seroconversion is associated
with HBV-specific T cell reactivity of Th1 lymphocytes and the emergence of mutations
within HBV pre-core and core regions in paediatric patients. 57th AASLD. Boston,
MA. October 27-31, 2006. Abstract 49.
