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Inhibition of Autoimmune Tubulointerstitial Nephritis in Guinea Pigs by Heterologous Antisera Containing Anti-Idiotype Antibodies

C. Alan Brown, Kathleen Carey and Robert B. Colvin
J Immunol November 1, 1979, 123 (5) 2102-2107;
C. Alan Brown
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Kathleen Carey
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Robert B. Colvin
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Abstract

Strain XIII guinea pigs immunized with rabbit tubular basement membrane (TBM) develop a severe tubulointerstitial nephritis mediated by anti-TBM antibodies. Experiments were performed to determine whether heterologous antibodies to the anti-TBM antibodies (anti-idiotypes) could suppress this autoimmune disease. Anti-TBM antibodies were eluted from strain XIII kidneys with anti-TBM disease and were partially purified by ion exchange chromatography. Antisera to various fractions (I, IV, VI; corresponding to IgG2, IgG1+2, and IgG1, respectively) were raised in rabbits. The antisera were repeatedly absorbed with normal strain XIII serum to remove reactivity to normal IgG. Ten milliliters of the absorbed rabbit antisera or control sera were given i.p. to strain XIII animals at the same time they were sensitized with rabbit TBM and ovalbumin in complete Freund's adjuvant. After 14 days, control animals immunized with TBM, but given either no serum, normal rabbit serum, or antiserum raised against eluates from normal strain XIII kidneys, developed severe tubulointerstitial nephritis with 84.4 ± 5.8, 64.6 ± 9.8, and 96.2 ± 3.5% of the renal cortex involved, respectively. Animals given the anti-idiotype sera had significantly less disease, with 12.6 ± 8.3 (VI), 16.5 ± 5.1 (IV), and 31.2 ± 10.4% (I) of the cortex affected. These animals also had significantly reduced levels of anti-TBM antibodies as measured by a solid phase radioimmunoassay. The antibody response to ovalbumin and tuberculin skin test reactions were not affected. A radioimmunoassay was developed to determine whether the most active rabbit antisera (VI) had anti-idiotypic activity. These sera bound specifically to the iodinated fraction VI anti-TBM antibody eluate, and pre-absorption of the fraction VI with either anti-guinea pig IgG or by guinea pig TBM removed the reactivity with the rabbit antisera.

These results indicate that specific inhibition of an autoantibody response and its consequent disease can be achieved by means of antisera raised to the autoantibodies. The mechanism has not been established, but it is believed to be due to idiotype suppression. A similar approach might prove suitable in other autoimmune diseases.

Footnotes

  • ↵1 This work was supported by United States Public Health Service Grants R01 AM18729 and IF 32 AM0 53921. This work was presented in part at the 63rd Annual Meeting of the Federation of the American Societies for Experimental Biology, Dallas, Texas 1979.

  • Received June 5, 1979.
  • Accepted August 6, 1979.
  • Copyright © 1979 by The American Association of Immunologists, Inc.

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The Journal of Immunology
Vol. 123, Issue 5
1 Nov 1979
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Inhibition of Autoimmune Tubulointerstitial Nephritis in Guinea Pigs by Heterologous Antisera Containing Anti-Idiotype Antibodies
C. Alan Brown, Kathleen Carey, Robert B. Colvin
The Journal of Immunology November 1, 1979, 123 (5) 2102-2107;

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Inhibition of Autoimmune Tubulointerstitial Nephritis in Guinea Pigs by Heterologous Antisera Containing Anti-Idiotype Antibodies
C. Alan Brown, Kathleen Carey, Robert B. Colvin
The Journal of Immunology November 1, 1979, 123 (5) 2102-2107;
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