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. 1974 Feb 1;139(2):278–294. doi: 10.1084/jem.139.2.278

PERSISTENCE OF HAPTEN-ANTIBODY COMPLEXES IN THE CIRCULATION OF IMMUNIZED ANIMALS AFTER A SINGLE INTRAVENOUS INJECTION OF HAPTEN

Donald H Schmidt 1, Bette M Kaufman 1, Vincent P Butler Jr 1
PMCID: PMC2139521  PMID: 4129823

Abstract

To study the fate of a low molecular weight antigen (hapten) in the circulation of animals whose sera contain antibodies specific for that low molecular weight antigen, a single injection of digoxin-3H (0.4 mg/kg) was administered intravenously to 18 rabbits. Thirteen animals (nine nonimmunized and four immunized with bovine serum albumin) served as control animals. In five rabbits which had been immunized with a digoxin-bovine serum albumin conjugate and whose sera contained digoxin-specific antibodies, the mean 12-h serum digoxin concentration was 8,300 ng/ml (control: 92 ng/ml) and the mean serum concentration 12 mo after the single injection of digoxin-3H was 85 ng/ml. In digoxin-immunized rabbits, less than 10% of the digoxin-3H was excreted in the first 10 days (control: 77% recovered in urine and feces) and the mean biological half-life of digoxin, as calculated from serum digoxin-3H disappearance curves, was 72 days (control: 3.4 days). In sera of digoxin-immunized rabbits, more than 90% of the circulating digoxin-3H was immunoglobulin bound, as determined by the double-antibody and dextran-coated charcoal methods. The serum disappearance rate of 125I-antidigoxin antibodies was similar in nonimmunized and in immunized animals and in the presence or absence of digoxin. It is concluded that the biological half-life of a hapten may be markedly prolonged when the hapten is bound to specific antibody. The persistence of antibody-hapten complexes in the circulation suggests that these complexes may not be deposited in tissues and raises the possibility that low molecular weight determinants may be capable of preventing or reversing the deposition of immune complexes, containing macromolecular antigens, in the tissues of experimental animals and man.

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Selected References

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  1. BERSON S. A., YALOW R. S., BAUMAN A., ROTHSCHILD M. A., NEWERLY K. Insulin-I131 metabolism in human subjects: demonstration of insulin binding globulin in the circulation of insulin treated subjects. J Clin Invest. 1956 Feb;35(2):170–190. doi: 10.1172/JCI103262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BUTLER V. P., Jr, VAUGHAN J. H. HEMAGGLUTINATION BY RHEUMATOID FACTOR OF CELLS COATED WITH ANIMAL GAMMA GLOBULINS. Proc Soc Exp Biol Med. 1964 Jul;116:585–593. doi: 10.3181/00379727-116-29313. [DOI] [PubMed] [Google Scholar]
  3. Butler V. P., Jr, Chen J. P. Digoxin-specific antibodies. Proc Natl Acad Sci U S A. 1967 Jan;57(1):71–78. doi: 10.1073/pnas.57.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Campbell D. H. On the significance of inhibiting haptens. Ann N Y Acad Sci. 1970 Feb 13;169(1):105–107. doi: 10.1111/j.1749-6632.1970.tb55974.x. [DOI] [PubMed] [Google Scholar]
  5. Cathou R. E., Werner T. C. Hapten stabilization of antibody conformation. Biochemistry. 1970 Aug 4;9(16):3149–3155. doi: 10.1021/bi00818a006. [DOI] [PubMed] [Google Scholar]
  6. Cochrane C. G. Mechanisms involved in the deposition of immune complexes in tissues. J Exp Med. 1971 Sep 1;134(3 Pt 2):75s–89s. [PubMed] [Google Scholar]
  7. Curd J., Smith T. W., Jaton J. C., Haber E. The isolation of digoxin-specific antibody and its use in reversing the effects of digoxin. Proc Natl Acad Sci U S A. 1971 Oct;68(10):2401–2406. doi: 10.1073/pnas.68.10.2401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DIXON F. J., MAURER P. H. Fate of antibody following in vivo combination with specific antigen. Proc Soc Exp Biol Med. 1953 Nov;84(2):442–446. doi: 10.3181/00379727-84-20672. [DOI] [PubMed] [Google Scholar]
  9. DIXON F. J., TALMAGE D. W. Catabolism of I131 labelled bovine gamma globulin in immune and non-immune rabbits. Proc Soc Exp Biol Med. 1951 Oct;78(1):123–125. doi: 10.3181/00379727-78-18996. [DOI] [PubMed] [Google Scholar]
  10. DOHERTY J. E., PERKINS W. H., MITCHELL G. K. Tritiated digoxin studies in human subjects. Arch Intern Med. 1961 Oct;108:531–539. doi: 10.1001/archinte.1961.03620100023004. [DOI] [PubMed] [Google Scholar]
  11. De Vos-Cloetens C., Minsart-Baleriaux V., Urbain-Vansanten G. Possible relationships between antibodies and non-specific immunoglobulins simultaneously induced after antigenic stimulation. Immunology. 1971 Jun;20(6):955–962. [PMC free article] [PubMed] [Google Scholar]
  12. Doherty J. E., Hall W. H., Murphy M. L., Beard O. W. New information regarding digitalis metabolism. Chest. 1971 Apr;59(4):433–437. doi: 10.1378/chest.59.4.433. [DOI] [PubMed] [Google Scholar]
  13. ERLANGER B. F., BEISER S. M. ANTIBODIES SPECIFIC FOR RIBONUCLEOSIDES AND RIBONUCLEOTIDES AND THEIR REACTION WITH DNA. Proc Natl Acad Sci U S A. 1964 Jul;52:68–74. doi: 10.1073/pnas.52.1.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goodfriend T. L., Webster M. E., McGuire J. S. Complex effects of antibodies to polypeptide hormones. J Clin Endocrinol Metab. 1970 May;30(5):565–572. doi: 10.1210/jcem-30-5-565. [DOI] [PubMed] [Google Scholar]
  15. Grossberg A. L., Markus G., Pressman D. Change in antibody conformation induced by hapten. Proc Natl Acad Sci U S A. 1965 Sep;54(3):942–945. doi: 10.1073/pnas.54.3.942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. doi: 10.1210/jcem-25-10-1375. [DOI] [PubMed] [Google Scholar]
  17. Kekwick R. A. The serum proteins in multiple myelomatosis. Biochem J. 1940 Sep;34(8-9):1248–1257. doi: 10.1042/bj0341248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lightfoot R. W., Jr, Drusin R. E., Christian C. L. Properties of soluble immune complexes. J Immunol. 1970 Dec;105(6):1493–1500. [PubMed] [Google Scholar]
  19. MATTHEWS C. M. The theory of tracer experiments with 131I-labelled plasma proteins. Phys Med Biol. 1957 Jul;2(1):36–53. doi: 10.1088/0031-9155/2/1/305. [DOI] [PubMed] [Google Scholar]
  20. MORSE J. H., CHRISTIAN C. L. IMMUNOLOGICAL STUDIES OF THE 11S PROTEIN COMPONENT OF THE HUMAN COMPLEMENT SYSTEM. J Exp Med. 1964 Feb 1;119:195–209. doi: 10.1084/jem.119.2.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pincus T., Haberkern R., Christian C. L. Experimental chronic glomerulitis. J Exp Med. 1968 Apr 1;127(4):819–832. doi: 10.1084/jem.127.4.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schmidt D. H., Butler V. P., Jr Immunological protecion against dixin toxicity. J Clin Invest. 1971 Apr;50(4):866–871. doi: 10.1172/JCI106558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Smith T. W., Butler V. P., Jr, Haber E. Characterization of antibodies of high affinity and specificity for the digitalis glycoside digoxin. Biochemistry. 1970 Jan 20;9(2):331–337. doi: 10.1021/bi00804a020. [DOI] [PubMed] [Google Scholar]
  24. Smith T. W., Butler V. P., Jr, Haber E. Determination of therapeutic and toxic serum digoxin concentrations by radioimmunoassay. N Engl J Med. 1969 Nov 27;281(22):1212–1216. doi: 10.1056/NEJM196911272812203. [DOI] [PubMed] [Google Scholar]
  25. TOMASI T., KUNKEL H. G. ISOLATION OF 7S AND 19S GAMMA GLOBULINS. Methods Med Res. 1964;10:80–86. [PubMed] [Google Scholar]
  26. Valdes A. J., Senterfit L. B., Pollack A. D., Germuth F. G., Jr The effect of antigen excess on chronic immune complex glomerulonephritis. Johns Hopkins Med J. 1969 Jan;124(1):9–17. [PubMed] [Google Scholar]
  27. Waldmann T. A., Strober W. Metabolism of immunoglobulins. Prog Allergy. 1969;13:1–110. doi: 10.1159/000385919. [DOI] [PubMed] [Google Scholar]
  28. Watson J. F., Butler V. P., Jr Biologic activity of digoxin-specific antisera. J Clin Invest. 1972 Mar;51(3):638–648. doi: 10.1172/JCI106853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wells J. V., Fudenberg H. H. Metabolism of radio-iodinated IgG in patients with abnormal IgG levels. I. Hypergamma-globulinaemia. Clin Exp Immunol. 1971 Dec;9(6):761–774. [PMC free article] [PubMed] [Google Scholar]
  30. Wilson C. B., Dixon F. J. Quantitation of acute and chronic serum sickness in the rabbit. J Exp Med. 1971 Sep 1;134(3 Pt 2):7s–8s. [PubMed] [Google Scholar]

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