A potential trigger of nephritogenic anti-DNA antibodies in lupus nephritis

Yasuhiko Hirabayashi, Y. Oka, M. Tada, R. Takahashi, T. Ishii

Research output: Chapter in Book/Report/Conference proceedingConference contribution

4 Citations (Scopus)

Abstract

Anti-DNA antibodies play an essential role in the pathogenesis of lupus nephritis. Mammalian DNA alone, however, is poorly immunogenic. We speculated that the antigenic trigger for the production of human nephritogenic anti-DNA antibodies is a non-DNA substance. The cDNA library from peripheral blood lymphocytes (PBLs) of a patient with active lupus nephritis was screened using the single-chain Fv of a human monoclonal nephritogenic O-81 anti-DNA antibody in a two-hybrid system. A clone containing the gene of an endoplasmic reticulum (ER) stress-inducible protein, Herp, was obtained. The O-81 antibody bound to recombinant Herp protein synthesized by Escherichia coli. Immunization with Herp elicited both anti-double-stranded DNA (anti-dsDNA) and anti-single-stranded (anti-ssDNA) antibodies in BALB/c mice and formed deposits of IgG in renal glomeruli. Anti-DNA antibodies purified from SLE sera bound to Herp. Moreover, anti-Herp antibodies showed specific binding to DNA. Herp was spontaneously expressed in PBLs of patients with active SLE, but not in PBLs of healthy subjects. These results imply that an inducible intracellular self-protein represents a candidate trigger for human nephritogenic anti-DNA autoantibodies. Any cell stress causing ER stress, such as viral infection, ultraviolet radiation, and chemicals, might be responsible for anti-DNA antibody production via Herp.

Original languageEnglish
Title of host publicationAutoimmunity, Part D
Subtitle of host publicationAutoimmune Disease, Annus Mirabilis
PublisherBlackwell Publishing Inc.
Pages92-95
Number of pages4
ISBN (Print)157331708X, 9781573317085
DOIs
Publication statusPublished - 2007 Jun

Publication series

NameAnnals of the New York Academy of Sciences
Volume1108
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Anti-DNA antibody
  • Cell stress
  • Lupus nephritis
  • Molecular mimicry
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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  • Cite this

    Hirabayashi, Y., Oka, Y., Tada, M., Takahashi, R., & Ishii, T. (2007). A potential trigger of nephritogenic anti-DNA antibodies in lupus nephritis. In Autoimmunity, Part D: Autoimmune Disease, Annus Mirabilis (pp. 92-95). (Annals of the New York Academy of Sciences; Vol. 1108). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1422.010