α-actinin is a cross-reactive renal target for pathogenic anti-DNA aptibodies

Bisram Deocharan, Xiaoping Qing, Juan Lichauco, Chaim Putterman

Research output: Contribution to journalArticle

163 Citations (Scopus)

Abstract

Anti-DNA Abs commonly found in patients with systemic lupus erythematosus are thought to play an important pathogenic role in lupus nephritis. Anti-DNA Abs may contribute to renal disease by cross-reactivity with renal Ags, the identity of which remain elusive. To identify a target Ag for pathogenic anti-DNA Abs, we performed Western blotting and immunoprecipitations of mesangial cell lysates from the lupus-prone MRL-lpr/lpr mouse and a nonautoimmune BALB/c mouse with the pathogenic anti-DNA Ab R4A. We found that R4A (but not a nonpathogenic Ab mutant of R4A) binds to and immunoprecipitates a 100-kDa protein expressed on the cell surface and in lysates of MRL- lpr/lpr mesangial cells. DNase treatment of the lysate and of the R4A Ab did not effect binding, indicating that the binding of R4A to the 100-kDa protein was direct and not mediated by an antigenic bridge containing DNA. Binding was greatly diminished in BALB/c lysates, suggesting that Ag expression or availability at the level of the target organ may be a factor in determining susceptibility to lupus nephritis. Following identification of this 100-kDa protein as nonmuscle α-actinin, binding of R4A to α-actinin was confirmed by Western blot, ELISA, inhibition studies, and immunofluorescence. High titers of anti-α-actinin Abs were present in sera and kidney eluates of lupus mice with active nephritis. These results indicate that the nephritogenicity of some anti-DNA Abs may be mediated via cross -reactivity with α-actinin. Furthermore, variations in target Ag display between individuals may underlie differential susceptibility to anti-DNA Ab-induced renal disease.

Original languageEnglish (US)
Pages (from-to)3072-3078
Number of pages7
JournalJournal of Immunology
Volume168
Issue number6
StatePublished - Mar 15 2002

Fingerprint

Actinin
Kidney
DNA
Lupus Nephritis
Mesangial Cells
Western Blotting
Proteins
Deoxyribonucleases
Nephritis
Immunoprecipitation
Systemic Lupus Erythematosus
Fluorescent Antibody Technique
Enzyme-Linked Immunosorbent Assay
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

α-actinin is a cross-reactive renal target for pathogenic anti-DNA aptibodies. / Deocharan, Bisram; Qing, Xiaoping; Lichauco, Juan; Putterman, Chaim.

In: Journal of Immunology, Vol. 168, No. 6, 15.03.2002, p. 3072-3078.

Research output: Contribution to journalArticle

Deocharan, B, Qing, X, Lichauco, J & Putterman, C 2002, 'α-actinin is a cross-reactive renal target for pathogenic anti-DNA aptibodies', Journal of Immunology, vol. 168, no. 6, pp. 3072-3078.
Deocharan, Bisram ; Qing, Xiaoping ; Lichauco, Juan ; Putterman, Chaim. / α-actinin is a cross-reactive renal target for pathogenic anti-DNA aptibodies. In: Journal of Immunology. 2002 ; Vol. 168, No. 6. pp. 3072-3078.
@article{2f2a3812198c4ee3a2f8e9c8cda305af,
title = "α-actinin is a cross-reactive renal target for pathogenic anti-DNA aptibodies",
abstract = "Anti-DNA Abs commonly found in patients with systemic lupus erythematosus are thought to play an important pathogenic role in lupus nephritis. Anti-DNA Abs may contribute to renal disease by cross-reactivity with renal Ags, the identity of which remain elusive. To identify a target Ag for pathogenic anti-DNA Abs, we performed Western blotting and immunoprecipitations of mesangial cell lysates from the lupus-prone MRL-lpr/lpr mouse and a nonautoimmune BALB/c mouse with the pathogenic anti-DNA Ab R4A. We found that R4A (but not a nonpathogenic Ab mutant of R4A) binds to and immunoprecipitates a 100-kDa protein expressed on the cell surface and in lysates of MRL- lpr/lpr mesangial cells. DNase treatment of the lysate and of the R4A Ab did not effect binding, indicating that the binding of R4A to the 100-kDa protein was direct and not mediated by an antigenic bridge containing DNA. Binding was greatly diminished in BALB/c lysates, suggesting that Ag expression or availability at the level of the target organ may be a factor in determining susceptibility to lupus nephritis. Following identification of this 100-kDa protein as nonmuscle α-actinin, binding of R4A to α-actinin was confirmed by Western blot, ELISA, inhibition studies, and immunofluorescence. High titers of anti-α-actinin Abs were present in sera and kidney eluates of lupus mice with active nephritis. These results indicate that the nephritogenicity of some anti-DNA Abs may be mediated via cross -reactivity with α-actinin. Furthermore, variations in target Ag display between individuals may underlie differential susceptibility to anti-DNA Ab-induced renal disease.",
author = "Bisram Deocharan and Xiaoping Qing and Juan Lichauco and Chaim Putterman",
year = "2002",
month = "3",
day = "15",
language = "English (US)",
volume = "168",
pages = "3072--3078",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

TY - JOUR

T1 - α-actinin is a cross-reactive renal target for pathogenic anti-DNA aptibodies

AU - Deocharan, Bisram

AU - Qing, Xiaoping

AU - Lichauco, Juan

AU - Putterman, Chaim

PY - 2002/3/15

Y1 - 2002/3/15

N2 - Anti-DNA Abs commonly found in patients with systemic lupus erythematosus are thought to play an important pathogenic role in lupus nephritis. Anti-DNA Abs may contribute to renal disease by cross-reactivity with renal Ags, the identity of which remain elusive. To identify a target Ag for pathogenic anti-DNA Abs, we performed Western blotting and immunoprecipitations of mesangial cell lysates from the lupus-prone MRL-lpr/lpr mouse and a nonautoimmune BALB/c mouse with the pathogenic anti-DNA Ab R4A. We found that R4A (but not a nonpathogenic Ab mutant of R4A) binds to and immunoprecipitates a 100-kDa protein expressed on the cell surface and in lysates of MRL- lpr/lpr mesangial cells. DNase treatment of the lysate and of the R4A Ab did not effect binding, indicating that the binding of R4A to the 100-kDa protein was direct and not mediated by an antigenic bridge containing DNA. Binding was greatly diminished in BALB/c lysates, suggesting that Ag expression or availability at the level of the target organ may be a factor in determining susceptibility to lupus nephritis. Following identification of this 100-kDa protein as nonmuscle α-actinin, binding of R4A to α-actinin was confirmed by Western blot, ELISA, inhibition studies, and immunofluorescence. High titers of anti-α-actinin Abs were present in sera and kidney eluates of lupus mice with active nephritis. These results indicate that the nephritogenicity of some anti-DNA Abs may be mediated via cross -reactivity with α-actinin. Furthermore, variations in target Ag display between individuals may underlie differential susceptibility to anti-DNA Ab-induced renal disease.

AB - Anti-DNA Abs commonly found in patients with systemic lupus erythematosus are thought to play an important pathogenic role in lupus nephritis. Anti-DNA Abs may contribute to renal disease by cross-reactivity with renal Ags, the identity of which remain elusive. To identify a target Ag for pathogenic anti-DNA Abs, we performed Western blotting and immunoprecipitations of mesangial cell lysates from the lupus-prone MRL-lpr/lpr mouse and a nonautoimmune BALB/c mouse with the pathogenic anti-DNA Ab R4A. We found that R4A (but not a nonpathogenic Ab mutant of R4A) binds to and immunoprecipitates a 100-kDa protein expressed on the cell surface and in lysates of MRL- lpr/lpr mesangial cells. DNase treatment of the lysate and of the R4A Ab did not effect binding, indicating that the binding of R4A to the 100-kDa protein was direct and not mediated by an antigenic bridge containing DNA. Binding was greatly diminished in BALB/c lysates, suggesting that Ag expression or availability at the level of the target organ may be a factor in determining susceptibility to lupus nephritis. Following identification of this 100-kDa protein as nonmuscle α-actinin, binding of R4A to α-actinin was confirmed by Western blot, ELISA, inhibition studies, and immunofluorescence. High titers of anti-α-actinin Abs were present in sera and kidney eluates of lupus mice with active nephritis. These results indicate that the nephritogenicity of some anti-DNA Abs may be mediated via cross -reactivity with α-actinin. Furthermore, variations in target Ag display between individuals may underlie differential susceptibility to anti-DNA Ab-induced renal disease.

UR - http://www.scopus.com/inward/record.url?scp=0037087262&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037087262&partnerID=8YFLogxK

M3 - Article

VL - 168

SP - 3072

EP - 3078

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -