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. 1983 Nov;42(2):585–593. doi: 10.1128/iai.42.2.585-593.1983

Circulating immune complexes in experimental syphilis: identification of treponemal antigens and specific antibodies to treponemal antigens in isolated complexes.

R E Baughn, C B Adams, D M Musher
PMCID: PMC264468  PMID: 6358026

Abstract

As a prelude to characterization of the host and treponemal antigens present in purified immune complexes from the sera of rabbits with disseminated syphilis, autoradiographic and immunoenzymatic analyses of solubilized extracts of Treponema pallidum, Treponema phagedenis biotype Reiter, and Treponema refringens were performed on electroblots of polypeptides first separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Electroblots of purified immune complexes were developed with the same panel of antisera so that protein profiles could be compared. Eight treponemal antigens were consistently present in isolated complexes; four of these cross-reacted with antisera prepared against avirulent treponemes. The average molecular weights of these antigens were 87,000, 76,000, 66,000, and 45,000. Antibodies dissociated from isolated immune complexes, when used for the development of T. pallidum electroblots, reacted with four antigens of comparable molecular weight. Antibodies to those polypeptides were also present in the sera of animals immunized with immune complexes. The demonstration of treponemal antigens in purified immune complexes convincingly argues that their occurrence in experimental syphilis is not merely due to tissue destruction and responses to endogenous host antigens.

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Selected References

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

  1. Alderete J. F., Baseman J. B. Analysis of serum IgG against Treponema pallidum protein antigens in experimentally infected rabbits. Br J Vener Dis. 1981 Oct;57(5):302–308. doi: 10.1136/sti.57.5.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alderete J. F., Baseman J. B. Surface characterization of virulent Treponema pallidum. Infect Immun. 1980 Dec;30(3):814–823. doi: 10.1128/iai.30.3.814-823.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Alderete J. F., Baseman J. B. Surface-associated host proteins on virulent Treponema pallidum. Infect Immun. 1979 Dec;26(3):1048–1056. doi: 10.1128/iai.26.3.1048-1056.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baseman J. B., Hayes E. C. Molecular characterization of receptor binding proteins and immunogens of virulent Treponema pallidum. J Exp Med. 1980 Mar 1;151(3):573–586. doi: 10.1084/jem.151.3.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baughn R. E., Adams C. B., Musher D. M. Immune complexes in experimental syphilis: a methodologic evaluation. Sex Transm Dis. 1982 Oct-Dec;9(4):170–177. doi: 10.1097/00007435-198210000-00002. [DOI] [PubMed] [Google Scholar]
  6. Baughn R. E., Musher D. M. Isolation and preliminary characterization of circulating immune complexes from rabbits with experimental syphilis. Infect Immun. 1983 Nov;42(2):579–584. doi: 10.1128/iai.42.2.579-584.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Baughn R. E., Tung K. S., Musher D. M. Detection of circulating immune complexes in the sera of rabbits with experimental syphilis: possible role in immunoregulation. Infect Immun. 1980 Aug;29(2):575–582. doi: 10.1128/iai.29.2.575-582.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bhorade M. S., Carag H. B., Lee H. J., Potter E. V., Dunea G. Nephropathy of secondary syphilis. A clinical and pathological spectrum. JAMA. 1971 May 17;216(7):1159–1166. [PubMed] [Google Scholar]
  9. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  10. Braunstein G. D., Lewis E. J., Galvanek E. G., Hamilton A., Bell W. R. The nephrotic syndrome associated with secondary syphilis. An immune deposit disease. Am J Med. 1970 May;48(5):643–648. doi: 10.1016/0002-9343(70)90016-1. [DOI] [PubMed] [Google Scholar]
  11. Digeon M., Laver M., Riza J., Bach J. F. Detection of circulating immune complexes in human sera by simplified assays with polyethylene glycol. J Immunol Methods. 1977;16(2):165–183. doi: 10.1016/0022-1759(77)90051-5. [DOI] [PubMed] [Google Scholar]
  12. Engel S., Diezel W. Persistent serum immune complexes in syphilis. Br J Vener Dis. 1980 Aug;56(4):221–222. doi: 10.1136/sti.56.4.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Falls W. F., Jr, Ford K. L., Ashworth C. T., Carter N. W. The nephrotic syndrome in secondary syphilis: report of a case with renal biopsy findings. Ann Intern Med. 1965 Dec;63(6):1047–1058. doi: 10.7326/0003-4819-63-6-1047. [DOI] [PubMed] [Google Scholar]
  14. Gamble C. N., Reardan J. B. Immunopathogenesis of syphilitic glomerulonephritis. Elution of antitreponemal antibody from glomerular immune-complex deposits. N Engl J Med. 1975 Feb 27;292(9):449–454. doi: 10.1056/NEJM197502272920903. [DOI] [PubMed] [Google Scholar]
  15. Guesdon J. L., Avrameas S. Polyacrylamide-agarose beads for the preparation of effective immunoabsorbents. J Immunol Methods. 1976;11(2):129–133. doi: 10.1016/0022-1759(76)90140-x. [DOI] [PubMed] [Google Scholar]
  16. Gurd J. W., Evans W. H. Identification of liver plasma membrane glycoproteins which bind to 125I-labelled concanavalin A following electrophoresis in sodium dodecyl sulfate. Can J Biochem. 1976 May;54(5):477–480. doi: 10.1139/o76-068. [DOI] [PubMed] [Google Scholar]
  17. Hanff P. A., Fehniger T. E., Miller J. N., Lovett M. A. Humoral immune response in human syphilis to polypeptides of Treponema pallidum. J Immunol. 1982 Sep;129(3):1287–1291. [PubMed] [Google Scholar]
  18. Hanff P. A., Miller J. N., Lovett M. A. Molecular characterization of common treponemal antigens. Infect Immun. 1983 May;40(2):825–828. doi: 10.1128/iai.40.2.825-828.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hardy P. H., Jr, Fredericks W. R., Nell E. E. Isolation and antigenic characteristics of axial filaments from the Reiter Treponeme. Infect Immun. 1975 Feb;11(2):380–386. doi: 10.1128/iai.11.2.380-386.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Harkiss G. D., Brown D. L. Detection of immune complexes by a new assay, the polyethylene glycol precipitation-complement consumption test (PEG-CC). Clin Exp Immunol. 1979 Apr;36(1):117–129. [PMC free article] [PubMed] [Google Scholar]
  21. Hellier M. D., Webster A. D., Eisinger A. J. Nephrotic syndrome: a complication of secondary syphilis. Br Med J. 1971 Nov 13;4(5784):404–405. doi: 10.1136/bmj.4.5784.404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Inman R. D., McDougal J. S., Redecha P. B., Lockshin M. D., Stevens C. E., Christian C. L. Isolation and characterization of circulating immune complexes in patients with hepatitis B systemic vasculitis. Clin Immunol Immunopathol. 1981 Dec;21(3):364–374. doi: 10.1016/0090-1229(81)90225-7. [DOI] [PubMed] [Google Scholar]
  23. Inman R. D., Redecha P. B., Knechtle S. J., Schned E. S., van de Rijn I., Christian C. L. Identification of bacterial antigens in circulating immune complexes of infective endocarditis. J Clin Invest. 1982 Aug;70(2):271–280. doi: 10.1172/JCI110614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Izzat N. N., Knox J. M., Wende R. D. Mass cultivation of avirulent Treponema pallidum (Nichols). Microbios. 1971 Apr;3(12):247–254. [PubMed] [Google Scholar]
  25. Kaplan B. S., Wiglesworth F. W., Marks M. I., Drummond K. N. The glomerulopathy of congenital syphilis--an immune deposit disease. J Pediatr. 1972 Dec;81(6):1154–1156. doi: 10.1016/s0022-3476(72)80251-8. [DOI] [PubMed] [Google Scholar]
  26. Kindt T. J. Rabbit immunoglobulin allotypes: structure, immunology, and genetics. Adv Immunol. 1975;21:35–86. doi: 10.1016/s0065-2776(08)60218-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  28. Lassus A., Förström L., Piha H. J., Kiistala U. Anticomplementary reactions and their relation to some auto-immune phenomena in syphilitic infection. Acta Derm Venereol. 1969;49(5):519–523. [PubMed] [Google Scholar]
  29. Lukehart S. A., Baker-Zander S. A., Gubish E. R., Jr Identification of Treponema pallidum antigens: comparison with a nonpathogenic treponeme. J Immunol. 1982 Aug;129(2):833–838. [PubMed] [Google Scholar]
  30. Miller J. N., Bekker J. H., DeBruijn J. H., Onvlee P. C. Antigenic structure of Treponema pallidum, Nichols strain. II. Extraction of a polysaccharide antigen with "strain-specific" serological activity. J Bacteriol. 1969 Jul;99(1):132–135. doi: 10.1128/jb.99.1.132-135.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Miller J. N., de Bruijn J. H., Bekker J. H., Onvlee P. C. The antigenic structure of Treponema pallidum, Nichols strain. I. The demonstration, nature and location of specific and shared antigens. J Immunol. 1966 Mar;96(3):450–456. [PubMed] [Google Scholar]
  32. Natali P. G., Walker L., Pellegrino M. A. Isolation of soluble immune complexes from serum using protein A bearing Staphylococcus aureus bacteria: separation of the antigen from immune complex and production of antisera. Clin Immunol Immunopathol. 1980 Jan;15(1):76–87. doi: 10.1016/0090-1229(80)90022-7. [DOI] [PubMed] [Google Scholar]
  33. Pedersen N. S., Axelsen N. H., Jørgensen B. B., Petersen C. S. Antibodies in secondary syphilis against five of forty Reiter treponeme antigens. Scand J Immunol. 1980;11(6):629–633. doi: 10.1111/j.1365-3083.1980.tb00031.x. [DOI] [PubMed] [Google Scholar]
  34. Pedersen N. S., Axelsen N. H., Petersen C. S. Antigenic analysis of Treponema pallidum: cross-reactions between individual antigens of T. pallidum and T. Reiter. Scand J Immunol. 1981;13(2):143–150. doi: 10.1111/j.1365-3083.1981.tb00120.x. [DOI] [PubMed] [Google Scholar]
  35. Penn C. W., Rhodes J. G. Surface-associated antigens of Treponema pallidum concealed by an inert outer layer. Immunology. 1982 May;46(1):9–16. [PMC free article] [PubMed] [Google Scholar]
  36. Petersen C. S., Pedersen N. S., Axelsen N. H. Purification of a Reiter treponemal protein antigen that is immunologically related to an antigen in Treponema pallidum. Infect Immun. 1982 Mar;35(3):974–978. doi: 10.1128/iai.35.3.974-978.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sølling J., Sølling K., Jacobsen K. U., Olsen S., From E. Circulating immune complexes in syphilitic nephropathy. A case report. Br J Vener Dis. 1978 Feb;54(1):53–56. doi: 10.1136/sti.54.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Tourville D. R., Byrd L. H., Kim D. U., Zajd D., Lee I., Reichman L. B., Baskin S. Treponemal antigen in immunopathogenesis of syphilitic glomerulonephritis. Am J Pathol. 1976 Mar;82(3):479–492. [PMC free article] [PubMed] [Google Scholar]
  39. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Weber K., Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem. 1969 Aug 25;244(16):4406–4412. [PubMed] [Google Scholar]
  41. Wozniczko-Orlowska G., Milgrom F. Immune complexes in syphilis sera. J Immunol. 1981 Sep;127(3):1048–1051. [PubMed] [Google Scholar]
  42. Young E. J., Weingarten N. M., Baughn R. E., Duncan W. C. Studies on the pathogenesis of the Jarisch-Herxheimer reaction: development of an animal model and evidence against a role for classical endotoxin. J Infect Dis. 1982 Nov;146(5):606–615. doi: 10.1093/infdis/146.5.606. [DOI] [PubMed] [Google Scholar]
  43. Yuceoglu A. M., Sagel I., Tresser G., Wasserman E., Lange K. The glomerulopathy of congenital syphilis. A curable immune-deposit disease. JAMA. 1974 Aug 19;229(8):1085–1089. [PubMed] [Google Scholar]

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