Polyreactive autoantibodies are nephritogenic in murine lupus nephritis

O. G. Pankewycz, P. Migliorini, Michael P. Madaio

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

To characterize the antibodies that form glomerular immune deposits in lupus nephritis, immunoglobulin (Ig) was eluted from the perfused kidney cortices of female MLR-lpr/lpr mice with early nephritis. The eluted Ig was predominantly IgG with antibody activity against DNA, multiple polynucleotides, SmRNP, gp70, and levan that was greater than the serum antibody activity of age- and sex-matched mice. Of particular interest, both kidney eluate and serum anti-DNA antibodies were observed to cross-react with multiple polynucleotides; however, only the kidney eluate Ig cross-reacted with phospholipids and RNA. Furthermore, the anti-DNA antibodies in the kidney eluate also cross-reacted with SmRNP and gp70; these ligand-binding properties were shared by the Ig in the kidney eluate that did not bind to DNA; and both kidney eluate fractions shared Id-H130 activity (a high frequency MRL-lpr/lpr idioptype). In contrast, the spectrotypes of Ig in the kidney eluate were found to be similar to serum, and they were observed to be between isoelectric points 6.5 to 7.8. Both the anti-DNA antibodies and the Ig that did not bind to DNA had similar isoelectric points throughout this entire range. These findings indicate that polyreactivity is a distinguishing feature of nephritogenic autoantibodies. They also raise the possibility that these ligand-binding properties influence the capacity of autoantibodies to form immune deposits. This influence could occur because polyreactive antibodies cross-react with antigenic determinants within the normal glomerular capillary wall. Alternatively, polyreactive antibodies may more readily form circulating immune complexes that are, in turn, passively trapped within the glomerulus.

Original languageEnglish (US)
Pages (from-to)3287-3294
Number of pages8
JournalJournal of Immunology
Volume139
Issue number10
StatePublished - Dec 1 1987
Externally publishedYes

Fingerprint

Lupus Nephritis
Autoantibodies
Immunoglobulins
Kidney
Antinuclear Antibodies
Antibodies
Polynucleotides
Isoelectric Point
DNA
Serum
Ligands
Kidney Cortex
Nephritis
Antigen-Antibody Complex
Epitopes
Phospholipids
Immunoglobulin G
RNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Pankewycz, O. G., Migliorini, P., & Madaio, M. P. (1987). Polyreactive autoantibodies are nephritogenic in murine lupus nephritis. Journal of Immunology, 139(10), 3287-3294.

Polyreactive autoantibodies are nephritogenic in murine lupus nephritis. / Pankewycz, O. G.; Migliorini, P.; Madaio, Michael P.

In: Journal of Immunology, Vol. 139, No. 10, 01.12.1987, p. 3287-3294.

Research output: Contribution to journalArticle

Pankewycz, OG, Migliorini, P & Madaio, MP 1987, 'Polyreactive autoantibodies are nephritogenic in murine lupus nephritis', Journal of Immunology, vol. 139, no. 10, pp. 3287-3294.
Pankewycz OG, Migliorini P, Madaio MP. Polyreactive autoantibodies are nephritogenic in murine lupus nephritis. Journal of Immunology. 1987 Dec 1;139(10):3287-3294.
Pankewycz, O. G. ; Migliorini, P. ; Madaio, Michael P. / Polyreactive autoantibodies are nephritogenic in murine lupus nephritis. In: Journal of Immunology. 1987 ; Vol. 139, No. 10. pp. 3287-3294.
@article{600c5f37bf074d6fa26850006b7e0850,
title = "Polyreactive autoantibodies are nephritogenic in murine lupus nephritis",
abstract = "To characterize the antibodies that form glomerular immune deposits in lupus nephritis, immunoglobulin (Ig) was eluted from the perfused kidney cortices of female MLR-lpr/lpr mice with early nephritis. The eluted Ig was predominantly IgG with antibody activity against DNA, multiple polynucleotides, SmRNP, gp70, and levan that was greater than the serum antibody activity of age- and sex-matched mice. Of particular interest, both kidney eluate and serum anti-DNA antibodies were observed to cross-react with multiple polynucleotides; however, only the kidney eluate Ig cross-reacted with phospholipids and RNA. Furthermore, the anti-DNA antibodies in the kidney eluate also cross-reacted with SmRNP and gp70; these ligand-binding properties were shared by the Ig in the kidney eluate that did not bind to DNA; and both kidney eluate fractions shared Id-H130 activity (a high frequency MRL-lpr/lpr idioptype). In contrast, the spectrotypes of Ig in the kidney eluate were found to be similar to serum, and they were observed to be between isoelectric points 6.5 to 7.8. Both the anti-DNA antibodies and the Ig that did not bind to DNA had similar isoelectric points throughout this entire range. These findings indicate that polyreactivity is a distinguishing feature of nephritogenic autoantibodies. They also raise the possibility that these ligand-binding properties influence the capacity of autoantibodies to form immune deposits. This influence could occur because polyreactive antibodies cross-react with antigenic determinants within the normal glomerular capillary wall. Alternatively, polyreactive antibodies may more readily form circulating immune complexes that are, in turn, passively trapped within the glomerulus.",
author = "Pankewycz, {O. G.} and P. Migliorini and Madaio, {Michael P.}",
year = "1987",
month = "12",
day = "1",
language = "English (US)",
volume = "139",
pages = "3287--3294",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - Polyreactive autoantibodies are nephritogenic in murine lupus nephritis

AU - Pankewycz, O. G.

AU - Migliorini, P.

AU - Madaio, Michael P.

PY - 1987/12/1

Y1 - 1987/12/1

N2 - To characterize the antibodies that form glomerular immune deposits in lupus nephritis, immunoglobulin (Ig) was eluted from the perfused kidney cortices of female MLR-lpr/lpr mice with early nephritis. The eluted Ig was predominantly IgG with antibody activity against DNA, multiple polynucleotides, SmRNP, gp70, and levan that was greater than the serum antibody activity of age- and sex-matched mice. Of particular interest, both kidney eluate and serum anti-DNA antibodies were observed to cross-react with multiple polynucleotides; however, only the kidney eluate Ig cross-reacted with phospholipids and RNA. Furthermore, the anti-DNA antibodies in the kidney eluate also cross-reacted with SmRNP and gp70; these ligand-binding properties were shared by the Ig in the kidney eluate that did not bind to DNA; and both kidney eluate fractions shared Id-H130 activity (a high frequency MRL-lpr/lpr idioptype). In contrast, the spectrotypes of Ig in the kidney eluate were found to be similar to serum, and they were observed to be between isoelectric points 6.5 to 7.8. Both the anti-DNA antibodies and the Ig that did not bind to DNA had similar isoelectric points throughout this entire range. These findings indicate that polyreactivity is a distinguishing feature of nephritogenic autoantibodies. They also raise the possibility that these ligand-binding properties influence the capacity of autoantibodies to form immune deposits. This influence could occur because polyreactive antibodies cross-react with antigenic determinants within the normal glomerular capillary wall. Alternatively, polyreactive antibodies may more readily form circulating immune complexes that are, in turn, passively trapped within the glomerulus.

AB - To characterize the antibodies that form glomerular immune deposits in lupus nephritis, immunoglobulin (Ig) was eluted from the perfused kidney cortices of female MLR-lpr/lpr mice with early nephritis. The eluted Ig was predominantly IgG with antibody activity against DNA, multiple polynucleotides, SmRNP, gp70, and levan that was greater than the serum antibody activity of age- and sex-matched mice. Of particular interest, both kidney eluate and serum anti-DNA antibodies were observed to cross-react with multiple polynucleotides; however, only the kidney eluate Ig cross-reacted with phospholipids and RNA. Furthermore, the anti-DNA antibodies in the kidney eluate also cross-reacted with SmRNP and gp70; these ligand-binding properties were shared by the Ig in the kidney eluate that did not bind to DNA; and both kidney eluate fractions shared Id-H130 activity (a high frequency MRL-lpr/lpr idioptype). In contrast, the spectrotypes of Ig in the kidney eluate were found to be similar to serum, and they were observed to be between isoelectric points 6.5 to 7.8. Both the anti-DNA antibodies and the Ig that did not bind to DNA had similar isoelectric points throughout this entire range. These findings indicate that polyreactivity is a distinguishing feature of nephritogenic autoantibodies. They also raise the possibility that these ligand-binding properties influence the capacity of autoantibodies to form immune deposits. This influence could occur because polyreactive antibodies cross-react with antigenic determinants within the normal glomerular capillary wall. Alternatively, polyreactive antibodies may more readily form circulating immune complexes that are, in turn, passively trapped within the glomerulus.

UR - http://www.scopus.com/inward/record.url?scp=0023631415&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023631415&partnerID=8YFLogxK

M3 - Article

VL - 139

SP - 3287

EP - 3294

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -