Comparative study in situ immune deposit formation in active and passive Heymann nephritis

Michael P. Madaio, D. J. Salant, A. J. Cohen, S. Adler, W. G. Couser

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Direct binding of antibodies to fixed glomerular antigens is the principal mechanism of subepithelial immune deposit formation in experimental membranous nephropathy induced by injection of heterologous antibody to rat Fx1A (passive Heymann nephritis, PHN). In actively induced Heymann nephritis (autologous immune complex nephritis, AICN) the role of this in situ mechanism as opposed to circulating immune complex deposition has been debated. To examine this question we studied the deposit-forming characteristic of rat IgG eluted from AICN kidneys and compared the results to those obtained with heterologous (sheep) anti-Fx1A IgG. We made the following observations: (1) AICN eluate IgG binds in vitro to proximal tubular brush borders and capillary walls of isolated glomeruli by immunofluorescence. Furthermore, 125I AICN eluate IgG binds specifically to isolated glomeruli (AICN eluate > 8 x control IgG). (2) After a single intravenous injection of 125I AICN eluate IgG, antibody continued to accumulate slowly in glomeruli over 48 hr. This pattern of antibody uptake closely resembles that previously described by us as unique for heterologous anti-TxIA. (3) Heterologous anti-Fx1A appeared to competitively inhibit the glomerular binding of AICN eluate IgG. When glomeruli containing increasing amounts of in vivo deposited 125I heterologous antibody were isolated and incubated with a fixed quantity of 131I AICN eluate IgG, an inverse relationship between the binding of the two antibodies was observed (r = -0.573, P <0.01). (4) Specific glomerular binding of AICN eluate IgG was observed in paired-label studies using the isolated perfused kidney (IPK). This confirms previous experiments in the IPK using heterologous antisera and demonstrates the capacity of AICN eluate IgG to form glomerular deposits in situ under relatively physiological conditions. We conclude that antibodies eluted from AICN glomeruli demonstrate deposit-forming characteristics very similar to those of heterologous anti-Fx1A antibodies in vitro and in vivo. Both antibodies produce subepithelial deposits in vivo and appear to bind to similar antigenic sites in the glomerular capillary wall. These results support the contention that in AICN, subepithelial immune deposit formation probably occurs by the same in situ mechanism previously demonstrated in PHN.

Original languageEnglish (US)
Pages (from-to)498-505
Number of pages8
JournalUnknown Journal
Volume23
Issue number3
DOIs
StatePublished - Jan 1 1983

Fingerprint

Membranous Glomerulonephritis
Nephritis
Antigen-Antibody Complex
experiment
Immunoglobulin G
Heterophile Antibodies
Antibodies
Kidney
Microvilli
Intravenous Injections
Fluorescent Antibody Technique
Immune Sera
Anti-Idiotypic Antibodies
Sheep

ASJC Scopus subject areas

  • Nephrology

Cite this

Madaio, M. P., Salant, D. J., Cohen, A. J., Adler, S., & Couser, W. G. (1983). Comparative study in situ immune deposit formation in active and passive Heymann nephritis. Unknown Journal, 23(3), 498-505. https://doi.org/10.1038/ki.1983.47

Comparative study in situ immune deposit formation in active and passive Heymann nephritis. / Madaio, Michael P.; Salant, D. J.; Cohen, A. J.; Adler, S.; Couser, W. G.

In: Unknown Journal, Vol. 23, No. 3, 01.01.1983, p. 498-505.

Research output: Contribution to journalArticle

Madaio, MP, Salant, DJ, Cohen, AJ, Adler, S & Couser, WG 1983, 'Comparative study in situ immune deposit formation in active and passive Heymann nephritis', Unknown Journal, vol. 23, no. 3, pp. 498-505. https://doi.org/10.1038/ki.1983.47
Madaio, Michael P. ; Salant, D. J. ; Cohen, A. J. ; Adler, S. ; Couser, W. G. / Comparative study in situ immune deposit formation in active and passive Heymann nephritis. In: Unknown Journal. 1983 ; Vol. 23, No. 3. pp. 498-505.
@article{28ce812d491547988413c4be72ee9477,
title = "Comparative study in situ immune deposit formation in active and passive Heymann nephritis",
abstract = "Direct binding of antibodies to fixed glomerular antigens is the principal mechanism of subepithelial immune deposit formation in experimental membranous nephropathy induced by injection of heterologous antibody to rat Fx1A (passive Heymann nephritis, PHN). In actively induced Heymann nephritis (autologous immune complex nephritis, AICN) the role of this in situ mechanism as opposed to circulating immune complex deposition has been debated. To examine this question we studied the deposit-forming characteristic of rat IgG eluted from AICN kidneys and compared the results to those obtained with heterologous (sheep) anti-Fx1A IgG. We made the following observations: (1) AICN eluate IgG binds in vitro to proximal tubular brush borders and capillary walls of isolated glomeruli by immunofluorescence. Furthermore, 125I AICN eluate IgG binds specifically to isolated glomeruli (AICN eluate > 8 x control IgG). (2) After a single intravenous injection of 125I AICN eluate IgG, antibody continued to accumulate slowly in glomeruli over 48 hr. This pattern of antibody uptake closely resembles that previously described by us as unique for heterologous anti-TxIA. (3) Heterologous anti-Fx1A appeared to competitively inhibit the glomerular binding of AICN eluate IgG. When glomeruli containing increasing amounts of in vivo deposited 125I heterologous antibody were isolated and incubated with a fixed quantity of 131I AICN eluate IgG, an inverse relationship between the binding of the two antibodies was observed (r = -0.573, P <0.01). (4) Specific glomerular binding of AICN eluate IgG was observed in paired-label studies using the isolated perfused kidney (IPK). This confirms previous experiments in the IPK using heterologous antisera and demonstrates the capacity of AICN eluate IgG to form glomerular deposits in situ under relatively physiological conditions. We conclude that antibodies eluted from AICN glomeruli demonstrate deposit-forming characteristics very similar to those of heterologous anti-Fx1A antibodies in vitro and in vivo. Both antibodies produce subepithelial deposits in vivo and appear to bind to similar antigenic sites in the glomerular capillary wall. These results support the contention that in AICN, subepithelial immune deposit formation probably occurs by the same in situ mechanism previously demonstrated in PHN.",
author = "Madaio, {Michael P.} and Salant, {D. J.} and Cohen, {A. J.} and S. Adler and Couser, {W. G.}",
year = "1983",
month = "1",
day = "1",
doi = "10.1038/ki.1983.47",
language = "English (US)",
volume = "23",
pages = "498--505",
journal = "Handbook of Behavioral Neuroscience",
issn = "0003-1348",
publisher = "JAI Press",
number = "3",

}

TY - JOUR

T1 - Comparative study in situ immune deposit formation in active and passive Heymann nephritis

AU - Madaio, Michael P.

AU - Salant, D. J.

AU - Cohen, A. J.

AU - Adler, S.

AU - Couser, W. G.

PY - 1983/1/1

Y1 - 1983/1/1

N2 - Direct binding of antibodies to fixed glomerular antigens is the principal mechanism of subepithelial immune deposit formation in experimental membranous nephropathy induced by injection of heterologous antibody to rat Fx1A (passive Heymann nephritis, PHN). In actively induced Heymann nephritis (autologous immune complex nephritis, AICN) the role of this in situ mechanism as opposed to circulating immune complex deposition has been debated. To examine this question we studied the deposit-forming characteristic of rat IgG eluted from AICN kidneys and compared the results to those obtained with heterologous (sheep) anti-Fx1A IgG. We made the following observations: (1) AICN eluate IgG binds in vitro to proximal tubular brush borders and capillary walls of isolated glomeruli by immunofluorescence. Furthermore, 125I AICN eluate IgG binds specifically to isolated glomeruli (AICN eluate > 8 x control IgG). (2) After a single intravenous injection of 125I AICN eluate IgG, antibody continued to accumulate slowly in glomeruli over 48 hr. This pattern of antibody uptake closely resembles that previously described by us as unique for heterologous anti-TxIA. (3) Heterologous anti-Fx1A appeared to competitively inhibit the glomerular binding of AICN eluate IgG. When glomeruli containing increasing amounts of in vivo deposited 125I heterologous antibody were isolated and incubated with a fixed quantity of 131I AICN eluate IgG, an inverse relationship between the binding of the two antibodies was observed (r = -0.573, P <0.01). (4) Specific glomerular binding of AICN eluate IgG was observed in paired-label studies using the isolated perfused kidney (IPK). This confirms previous experiments in the IPK using heterologous antisera and demonstrates the capacity of AICN eluate IgG to form glomerular deposits in situ under relatively physiological conditions. We conclude that antibodies eluted from AICN glomeruli demonstrate deposit-forming characteristics very similar to those of heterologous anti-Fx1A antibodies in vitro and in vivo. Both antibodies produce subepithelial deposits in vivo and appear to bind to similar antigenic sites in the glomerular capillary wall. These results support the contention that in AICN, subepithelial immune deposit formation probably occurs by the same in situ mechanism previously demonstrated in PHN.

AB - Direct binding of antibodies to fixed glomerular antigens is the principal mechanism of subepithelial immune deposit formation in experimental membranous nephropathy induced by injection of heterologous antibody to rat Fx1A (passive Heymann nephritis, PHN). In actively induced Heymann nephritis (autologous immune complex nephritis, AICN) the role of this in situ mechanism as opposed to circulating immune complex deposition has been debated. To examine this question we studied the deposit-forming characteristic of rat IgG eluted from AICN kidneys and compared the results to those obtained with heterologous (sheep) anti-Fx1A IgG. We made the following observations: (1) AICN eluate IgG binds in vitro to proximal tubular brush borders and capillary walls of isolated glomeruli by immunofluorescence. Furthermore, 125I AICN eluate IgG binds specifically to isolated glomeruli (AICN eluate > 8 x control IgG). (2) After a single intravenous injection of 125I AICN eluate IgG, antibody continued to accumulate slowly in glomeruli over 48 hr. This pattern of antibody uptake closely resembles that previously described by us as unique for heterologous anti-TxIA. (3) Heterologous anti-Fx1A appeared to competitively inhibit the glomerular binding of AICN eluate IgG. When glomeruli containing increasing amounts of in vivo deposited 125I heterologous antibody were isolated and incubated with a fixed quantity of 131I AICN eluate IgG, an inverse relationship between the binding of the two antibodies was observed (r = -0.573, P <0.01). (4) Specific glomerular binding of AICN eluate IgG was observed in paired-label studies using the isolated perfused kidney (IPK). This confirms previous experiments in the IPK using heterologous antisera and demonstrates the capacity of AICN eluate IgG to form glomerular deposits in situ under relatively physiological conditions. We conclude that antibodies eluted from AICN glomeruli demonstrate deposit-forming characteristics very similar to those of heterologous anti-Fx1A antibodies in vitro and in vivo. Both antibodies produce subepithelial deposits in vivo and appear to bind to similar antigenic sites in the glomerular capillary wall. These results support the contention that in AICN, subepithelial immune deposit formation probably occurs by the same in situ mechanism previously demonstrated in PHN.

UR - http://www.scopus.com/inward/record.url?scp=0020529281&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020529281&partnerID=8YFLogxK

U2 - 10.1038/ki.1983.47

DO - 10.1038/ki.1983.47

M3 - Article

C2 - 6221142

AN - SCOPUS:0020529281

VL - 23

SP - 498

EP - 505

JO - Handbook of Behavioral Neuroscience

JF - Handbook of Behavioral Neuroscience

SN - 0003-1348

IS - 3

ER -