Differential binding of cross-reactive anti-DNA antibodies to mesangial cells: The role of α-actinin

Zeguo Zhao, Bisram Deocharan, Philipp E. Scherer, Laurie J. Ozelius, Chaim Putterman

Research output: Contribution to journalArticle

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Abstract

Target Ag display is a necessary requirement for the expression of certain immune-mediated kidney diseases. We previously had shown that anti-DNA Abs that cross-react with α-actinin may be important in the pathogenesis of murine and human lupus nephritis; in murine models, we had found that a significant proportion of pathogenic serum and kidney-deposited Igs are α-actinin reactive. Furthermore, a pathogenic anti-DNA/α-actinin Ab showed enhanced binding to immortalized mesangial cells (MCs) derived from a lupus prone MRL-lpr/lpr mouse as compared with MCs from BALB/c mice which are not susceptible to spontaneous lupus, suggesting that kidney α-actinin expression may be contributing to nephritis. In the current study, we established that two isoforms of α-actinin that are present in the kidney, α-actinin 1 and α-actinin 4, can both be targeted by anti-α-actinin Abs. We found novel sequence polymorphisms between MRL-lpr/lpr and BALB/c in the gene for α-actinin 4. Moreover, α-actinin 4 and a splice variant of α-actinin 1 were both expressed at significantly higher levels (mRNA and protein) in MCs from the lupus prone MRL-lpr/lpr strain. Significantly, we were able to confirm these differences in intact kidney by examining glomerular Ig deposition of anti-α-actinin Abs. We conclude that enhanced α-actinin expression may determine the extent of Ig deposition in the Ab-mediated kidney disease in lupus. Modulation of Ag expression may be a promising approach to down-regulate immune complex formation in the target organ in individuals with circulating pathogenic Abs.

Original languageEnglish (US)
Pages (from-to)7704-7714
Number of pages11
JournalJournal of Immunology
Volume176
Issue number12
StatePublished - Jun 15 2006

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Actinin
Mesangial Cells
Antinuclear Antibodies
Kidney
Kidney Diseases
Lupus Nephritis
Nephritis
DNA
Antigen-Antibody Complex

ASJC Scopus subject areas

  • Immunology

Cite this

Differential binding of cross-reactive anti-DNA antibodies to mesangial cells : The role of α-actinin. / Zhao, Zeguo; Deocharan, Bisram; Scherer, Philipp E.; Ozelius, Laurie J.; Putterman, Chaim.

In: Journal of Immunology, Vol. 176, No. 12, 15.06.2006, p. 7704-7714.

Research output: Contribution to journalArticle

Zhao, Z, Deocharan, B, Scherer, PE, Ozelius, LJ & Putterman, C 2006, 'Differential binding of cross-reactive anti-DNA antibodies to mesangial cells: The role of α-actinin', Journal of Immunology, vol. 176, no. 12, pp. 7704-7714.
Zhao, Zeguo ; Deocharan, Bisram ; Scherer, Philipp E. ; Ozelius, Laurie J. ; Putterman, Chaim. / Differential binding of cross-reactive anti-DNA antibodies to mesangial cells : The role of α-actinin. In: Journal of Immunology. 2006 ; Vol. 176, No. 12. pp. 7704-7714.
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