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. 1991 Jun;84(3):493–500.

Analysis of viral proteins in circulating immune complexes from chronic carriers of hepatitis B virus.

K Madalinski 1, B Burczynska 1, K H Heermann 1, A Uy 1, W H Gerlich 1
PMCID: PMC1535435  PMID: 2044231

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alberti A., Gerlich W. H., Heermann K. H., Pontisso P. Nature and display of hepatitis B virus envelope proteins and the humoral immune response. Springer Semin Immunopathol. 1990;12(1):5–23. doi: 10.1007/BF00192678. [DOI] [PubMed] [Google Scholar]
  2. Anh-Tuan N., Novák E. Hepatitis B surface antigen circulating immune complexes (HBsAg-CICs) in patients with hepatitis B and asymptomatic HBsAg carriers. Clin Exp Immunol. 1981 Feb;43(2):246–253. [PMC free article] [PubMed] [Google Scholar]
  3. Brown S. E., Steward M. W., Viola L., Howard C. R., Murray-Lyon I. M. Chronic liver disease: the detection and characterization of circulating immune complexes. Immunology. 1983 Aug;49(4):673–683. [PMC free article] [PubMed] [Google Scholar]
  4. Bruss V., Gerlich W. H. Formation of transmembraneous hepatitis B e-antigen by cotranslational in vitro processing of the viral precore protein. Virology. 1988 Apr;163(2):268–275. doi: 10.1016/0042-6822(88)90266-8. [DOI] [PubMed] [Google Scholar]
  5. Careoda F., de Franchis R., D'Arminio Monforte A., Vecchi M., Rossi E., Primignani M., Palla M., Dioguardi N. Persistence of circulating HBsAg/IgM complexes in acute viral hepatitis, type B: an early marker of chronic evolution. Lancet. 1982 Aug 14;2(8294):358–360. doi: 10.1016/s0140-6736(82)90549-9. [DOI] [PubMed] [Google Scholar]
  6. Creighton W. D., Lambert P. H., Miescher P. A. Detection of antibodies and soluble antigen-antibody complexes by precipitation with polyethylene glycol. J Immunol. 1973 Oct;111(4):1219–1227. [PubMed] [Google Scholar]
  7. Deepen R., Heermann K. H., Uy A., Thomssen R., Gerlich W. H. Assay of preS epitopes and preS1 antibody in hepatitis B virus carriers and immune persons. Med Microbiol Immunol. 1990;179(1):49–60. doi: 10.1007/BF00190150. [DOI] [PubMed] [Google Scholar]
  8. Frisch-Niggemeyer W., Hofmann H., Kunz C. Frühzeitige Prognose des Verlaufs der Hepatitis B durch Radioimmunoassay von HBsAg/IgM-Komplexen. Wien Klin Wochenschr. 1984 Sep 28;96(18):669–673. [PubMed] [Google Scholar]
  9. Gerlich W. H., Uy A., Lambrecht F., Thomssen R. Cutoff levels of immunoglobulin M antibody against viral core antigen for differentiation of acute, chronic, and past hepatitis B virus infections. J Clin Microbiol. 1986 Aug;24(2):288–293. doi: 10.1128/jcm.24.2.288-293.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gerlich W., Thomssen R. Standardized detection of hepatitis B surface antigen: determination of its serum concentration in weight units per volume. Dev Biol Stand. 1975;30:78–87. [PubMed] [Google Scholar]
  11. Gregorek H., Jung H., Ułanowicz G., Madaliński K. Immune complexes in sera of children with HBV-mediated glomerulonephritis. Arch Immunol Ther Exp (Warsz) 1986;34(1):73–83. [PubMed] [Google Scholar]
  12. Gupta R. C., Kohler P. F. Identification of HBsAg determinants in immune complexes from hepatitis B virus-associated vasculitis. J Immunol. 1984 Mar;132(3):1223–1228. [PubMed] [Google Scholar]
  13. Gültekin H., Heermann K. H. The use of polyvinylidenedifluoride membranes as a general blotting matrix. Anal Biochem. 1988 Aug 1;172(2):320–329. doi: 10.1016/0003-2697(88)90451-4. [DOI] [PubMed] [Google Scholar]
  14. Heermann K. H., Goldmann U., Schwartz W., Seyffarth T., Baumgarten H., Gerlich W. H. Large surface proteins of hepatitis B virus containing the pre-s sequence. J Virol. 1984 Nov;52(2):396–402. doi: 10.1128/jvi.52.2.396-402.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Heermann K. H., Kruse F., Seifer M., Gerlich W. H. Immunogenicity of the gene S and Pre-S domains in hepatitis B virions and HBsAg filaments. Intervirology. 1987;28(1):14–25. doi: 10.1159/000149993. [DOI] [PubMed] [Google Scholar]
  16. Ito H., Hattori S., Matusda I., Amamiya S., Hajikano H., Yoshizawa H., Miyakawa Y., Mayumi M. Hepatitis B e antigen-mediated membranous glomerulonephritis. Correlation of ultrastructural changes with HBeAg in the serum and glomeruli. Lab Invest. 1981 Mar;44(3):214–220. [PubMed] [Google Scholar]
  17. Kaplan P. M., Greenman R. L., Gerin J. L., Purcell R. H., Robinson W. S. DNA polymerase associated with human hepatitis B antigen. J Virol. 1973 Nov;12(5):995–1005. doi: 10.1128/jvi.12.5.995-1005.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lambert P. H., Tribollet E., Celada A., Madalinski K., Frei P. C., Miescher P. A. Quantitation of immunoglobulin-associated HBs antigen in patients with acute and chronic hepatitis, in healthy carriers and in polyarteritis nodosa. J Clin Lab Immunol. 1980 Jan;3(1):1–8. [PubMed] [Google Scholar]
  19. Madaliński K., Bragiel I. HBsAg immune complexes in the course of infection with hepatitis B virus. Clin Exp Immunol. 1979 Jun;36(3):371–378. [PMC free article] [PubMed] [Google Scholar]
  20. Milich D. R., McLachlan A., Chisari F. V., Kent S. B., Thorton G. B. Immune response to the pre-S(1) region of the hepatitis B surface antigen (HBsAg): a pre-S(1)-specific T cell response can bypass nonresponsiveness to the pre-S(2) and S regions of HBsAg. J Immunol. 1986 Jul 1;137(1):315–322. [PubMed] [Google Scholar]
  21. Milich D. R., McLachlan A., Thornton G. B., Hughes J. L. Antibody production to the nucleocapsid and envelope of the hepatitis B virus primed by a single synthetic T cell site. Nature. 1987 Oct 8;329(6139):547–549. doi: 10.1038/329547a0. [DOI] [PubMed] [Google Scholar]
  22. Mondelli M., Vergani G. M., Alberti A., Vergani D., Portmann B., Eddleston A. L., Williams R. Specificity of T lymphocyte cytotoxicity to autologous hepatocytes in chronic hepatitis B virus infection: evidence that T cells are directed against HBV core antigen expressed on hepatocytes. J Immunol. 1982 Dec;129(6):2773–2778. [PubMed] [Google Scholar]
  23. Palla M., Rizzi R., Toti M., Almi P., Rizzetto M., Bonino F., Purcell R. Complexes of hepatitis B surface antigen and immunoglobulin M in the sera of patients with hepatitis B virus infection. Infect Immun. 1983 Sep;41(3):950–958. doi: 10.1128/iai.41.3.950-958.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pernice W., Sodomann C. P., Lüben G., Seiler F. R., Sedlacek H. H. Antigen-specific detection of HBsAG-containing immune complexes in the course of hepatitis B virus infection. Clin Exp Immunol. 1979 Aug;37(2):376–380. [PMC free article] [PubMed] [Google Scholar]
  25. Peterson D. L., Paul D. A., Lam J., Tribby I. I., Achord D. T. Antigenic structure of hepatitis B surface antigen: identification of the "d" subtype determinant by chemical modification and use of monoclonal antibodies. J Immunol. 1984 Feb;132(2):920–927. [PubMed] [Google Scholar]
  26. Rath S., Devey M. E. IgG subclass composition of antibodies to HBsAg in circulating immune complexes from patients with hepatitis B virus infections. Clin Exp Immunol. 1988 Apr;72(1):164–167. [PMC free article] [PubMed] [Google Scholar]
  27. Sansonno D. E., Detomaso P., Primavera M. V., Papanice M. A., Donnaloia R., Manghisi O. G. Demonstration of HBsAg as the antigen component in circulating immune complexes detected by peg-solid phase test. J Virol Methods. 1986 Sep;14(2):141–151. doi: 10.1016/0166-0934(86)90045-5. [DOI] [PubMed] [Google Scholar]
  28. Seifer M., Heermann K. H., Gerlich W. H. Expression pattern of the hepatitis B virus genome in transfected mouse fibroblasts. Virology. 1990 Nov;179(1):287–299. doi: 10.1016/0042-6822(90)90297-5. [DOI] [PubMed] [Google Scholar]
  29. Standring D. N., Ou J. H., Masiarz F. R., Rutter W. J. A signal peptide encoded within the precore region of hepatitis B virus directs the secretion of a heterogeneous population of e antigens in Xenopus oocytes. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8405–8409. doi: 10.1073/pnas.85.22.8405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Stibbe W., Gerlich W. H. Structural relationships between minor and major proteins of hepatitis B surface antigen. J Virol. 1983 May;46(2):626–628. doi: 10.1128/jvi.46.2.626-628.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Surelia P., Boxall E. H. Hepatitis B virus infection: detection of circulating HBsAg/IgM antibody immune complexes. Med Lab Sci. 1990 Jul;47(3):204–209. [PubMed] [Google Scholar]
  32. Takai E., Machida A., Ohnuma H., Miyamoto H., Tanaka T., Baba K., Tsuda F., Usuda S., Nakamura T., Miyakawa Y. A solid-phase enzyme immunoassay for the determination of IgM and IgG antibodies against translation products of pre-S1 and pre-S2 regions of hepatitis B virus. J Immunol Methods. 1986 Dec 4;95(1):23–30. doi: 10.1016/0022-1759(86)90313-3. [DOI] [PubMed] [Google Scholar]
  33. Uy A., Bruss V., Gerlich W. H., Köchel H. G., Thomssen R. Precore sequence of hepatitis B virus inducing e antigen and membrane association of the viral core protein. Virology. 1986 Nov;155(1):89–96. doi: 10.1016/0042-6822(86)90170-4. [DOI] [PubMed] [Google Scholar]
  34. Vento S., Chen S. H., Giuliani-Piccari G., O'Brien C. J., Dal Monte P. R., Eddleston A. L., Howard C. R., Williams R. Cellular immunity to nucleocapsid and pre-S determinants in asymptomatic carriers of hepatitis B virus. Immunology. 1987 Dec;62(4):593–598. [PMC free article] [PubMed] [Google Scholar]
  35. Zyzik E., Gerlich W. H., Uy A., Köchel H., Thomssen R. Assay of hepatitis B virus genome titers in sera of infected subjects. Eur J Clin Microbiol. 1986 Jun;5(3):330–335. doi: 10.1007/BF02017791. [DOI] [PubMed] [Google Scholar]

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