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

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

研究成果: Chapter in Book/Report/Conference proceedingConference contribution

5 被引用数 (Scopus)

抄録

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.

本文言語英語
ホスト出版物のタイトルAutoimmunity, Part D
ホスト出版物のサブタイトルAutoimmune Disease, Annus Mirabilis
出版社Blackwell Publishing Inc.
ページ92-95
ページ数4
ISBN(印刷版)157331708X, 9781573317085
DOI
出版ステータス出版済み - 6 2007

出版物シリーズ

名前Annals of the New York Academy of Sciences
1108
ISSN(印刷版)0077-8923
ISSN(電子版)1749-6632

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 科学史および科学哲学

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