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Analysis of viral proteins in circulating immune complexes from chronic carriers of hepatitis B virus
K Madalinski1, B Burczynska, K H Heermann
1Department of Immunology, Children's Memorial Hospital, Warsaw, Poland.
Insights
Immune complexes in children with chronic hepatitis B virus (HBV) infection primarily contain HBs proteins, not HBe proteins. High levels of HBs-containing immune complexes may predict HBV elimination, potentially initiated by anti-pre-S1 antibodies.
Area of Science:
- Hepatology
- Immunology
- Virology
Background:
- Chronic hepatitis B virus (HBV) infection affects numerous children worldwide.
- Understanding immune responses in chronic HBV is crucial for developing effective treatments.
- Immune complexes play a role in viral infections, but their specific composition and significance in pediatric HBV remain under investigation.
Purpose of the Study:
- To investigate the composition of immune complexes in children with chronic HBV infection.
- To determine the correlation between immune complex content and clinical outcomes.
- To explore the potential role of immune complexes in HBV elimination.
Main Methods:
- Sera from 54 children with chronic HBV infection were analyzed.
- Immune complexes were precipitated using polyethylene glycol (PEG).
- Immune complexes were characterized using immune blot with monoclonal antibodies against various HBV epitopes (S, pre-S2, pre-S1, HBe/c).
Main Results:
- All sera, including controls, contained PEG-precipitable substances, but amounts did not correlate with HBV protein levels.
- HBeAg-positive patients predominantly had HBs proteins, but not HBe proteins, in their immune complexes.
- Immune complexes often contained higher levels of pre-S1 than free HBsAg particles.
- Anti-HBe-positive patients rarely had HBV proteins in immune complexes, and in low amounts.
- High levels of HBs-containing immune complexes correlated with subsequent HBV elimination in six patients.
Conclusions:
- Immune complexes in children with chronic HBV are primarily composed of HBs proteins, with limited HBe protein presence.
- The composition of immune complexes may differ between HBeAg-positive and anti-HBe-positive individuals.
- Elevated HBs-containing immune complexes may serve as a marker for impending HBV clearance.
- Anti-pre-S1 antibodies might play a role in initiating HBV elimination by targeting HBV and HBs particles.
Abstract:
Sera from 54 children (mean age 5.8 years) with chronic hepatitis B virus (HBV) infection were investigated for the presence of immune complexes containing HBV proteins. Clinical diagnosis was established by histology and biochemical markers and included chronic persistent (36 cases) or chronic aggressive (seven) hepatitis, liver cirrhosis (six) and HBV-mediated membranous glomerulonephritis (five). Circulating immune complexes were precipitated with 2.5% polyethylene glycol and analysed by immune blot using monoclonal antibodies against S, pre-S2 glycopeptide, pre-S1 and HBe/c epitopes. All sera, including those from 11 healthy HBV-negative blood donors contained PEG-precipitable substances, but the amount of precipitate did not correlate with the presence or amount of HBV proteins. The great majority (36 out of 40) of HBeAg-positive patients contained HBs proteins in immune complexes, but no detectable HBe protein. The immune complexes usually contained more pre-S1 than the free HBsAg particles from the same patient. The precipitates of anti-HBe-positive patients rarely contained HBV proteins (two out of 14) and, if so, in low amounts. During follow up of six patients we found that high levels of HBs-containing immune complexes may be correlated with subsequent elimination of HBV. This elimination is possibly initiated by binding of anti-pre-S1 antibodies to HBV and HBs particles.