Experimental immune complex-mediated glomerulonephritis in the nonhuman primate

Lee A. Hebert, Fernando G Cosio, Daniel J. Birmingham, John D. Mahan, Hari M. Sharma, William L. Smead, Rajiv Goel

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Abstract

This study was undertaken to develop a model of immune complex (IC)-mediated glomerulonephritis (GN) in the nonhuman primate that could be used in subsequent studies to examine critically the role of the erythrocyte complement receptor (E-CR) in the pathogenesis of IC-mediated disease. Cynomolgus monkeys were chosen for study because they constituatively express E-CR levels that are either less than, equal to, or greater than that seen in normal man. After immunization with bovine gamma globulin (BGG), the GN induction protocol was begun in 10 cynomolgus by initiating daily i.v. administration of BGG in amounts sufficient to achieve or exceed antigen/ antibody equivalence (assessed by the quantitative precipitin assay) for precipitating antibody present in the plasma volume. We found that within eight weeks of daily BGG administration all of the cynomolgus developed IC-mediated GN, irrespective of the initial E-CR level of the animals. However, the high E-CR cynomolgus tended to receive the higher BGG doses because of higher initial antibody levels to BGG. When the total number of glomerular deposits (determined by morphometric studies) per total BGG dose for each animal was plotted against the initial CR/E of that animal, there was a tendency for the animals with higher CR/E levels to have a lower number of glomerular deposits/ BGG dose (r = 0.62, P = 0.06). Also, the total number of glomerular deposits correlated with the severity of the GN. During the early weeks of the GN induction protocol, the IC that formed in vivo (assessed by infusion of 125I-BGG) bound in large amounts to the circulating erythrocytes of the cynomolgus with medium or high E-CR levels. However, when tested after the onset of heavy proteinuria, which occurred between weeks 5 and 8 of daily BGG administration, the IC that formed in the circulation bound only poorly to circulating erythrocytes. By this time the E-CR levels had declined to 43 ± 9% of initial values (P < 0.01). This study demonstrates that: 1) A workable model of IC-mediated GN has been developed in the nonhuman primate. 2) During the induction of GN, CR/E and the ability of the erythrocyte to bind IC in vivo are decreased significantly. This suggests that an intact E-CR system could play a role in the protection against IC-mediated disease. However, further study will be needed to test that hypothesis critically. The present model should be useful in such studies.

Original languageEnglish (US)
Pages (from-to)44-56
Number of pages13
JournalKidney International
Volume39
Issue number1
StatePublished - Jan 1991
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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    Hebert, L. A., Cosio, F. G., Birmingham, D. J., Mahan, J. D., Sharma, H. M., Smead, W. L., & Goel, R. (1991). Experimental immune complex-mediated glomerulonephritis in the nonhuman primate. Kidney International, 39(1), 44-56.