α-actinin immunization elicits anti-chromatin autoimmunity in nonautoimmune mice

Bisram Deocharan, Zhijie Zhou, Kochnaf Antar, Linda Siconolfi-Baez, Ruth Hogue Angeletti, John Hardin, Chaim Putterman

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Anti-dsDNA Abs are characteristic of lupus and can be found deposited in the kidneys of lupus mice. Previously, we have shown that pathogenic anti-dsDNA Abs as well as Ig eluted from the kidneys of nephritic lupus mice cross-react with α-actinin. Moreover, cross-reactivity with α-actinin characterizes nephritogenic anti-dsDNA Abs in humans with lupus as well. To determine whether Abs generated against α-actinin in vivo cross-react with nuclear Ags, we s.c. immunized 10-wk-old female BALB/c mice (and several other nonautoimmune mice strains) with α-actinin in adjuvant. Immunized but not control mice displayed high titers of anti-nuclear Abs and IgG anti-chromatin autoantibodies, hypergammaglobulinemia, renal Ig deposition, and proteinuria. The specificity of the antichromatin response was determined by Western blotting of purified chromatin with serum from α-actinin immunized mice. By proteomic analysis, a 25-kDa doublet band was conclusively identified as high mobility group box (HMGB) proteins 1 and 3, and a 70-kDa band was identified as heat shock protein 70 (hsp70), both of which are known antigenic targets in murine lupus. Binding to purified HMGB1 and hsp70 by immunized mice sera was confirmed by ELISA and Western blot. Immunized mice sera binding to both 25- and 70-kDa bands were significantly inhibited by α-actinin and chromatin. Importantly, a panel of nephritogenic mAbs had significantly higher affinity for α-actinin, chromatin, HMGB, and hsp70 as compared with nonpathogenic Abs, suggesting a common motif in these Ags that is targeted by pathogenic autoantibodies.

Original languageEnglish (US)
Pages (from-to)1313-1321
Number of pages9
JournalJournal of Immunology
Volume179
Issue number2
StatePublished - Jul 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Deocharan, B., Zhou, Z., Antar, K., Siconolfi-Baez, L., Angeletti, R. H., Hardin, J., & Putterman, C. (2007). α-actinin immunization elicits anti-chromatin autoimmunity in nonautoimmune mice. Journal of Immunology, 179(2), 1313-1321.