Progression of lupus-like disease drives the appearance of complement-activating IgG antibodies in MRL/lpr mice

Krisztián Papp, Péter Végh, Andrey Tchorbanov, Tchavdar Vassilev, Anna Erdei, József Prechl

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objectives: Nucleic acids are known to induce complement activation, which results in the masking and removal of apoptotic cells exposing nuclear components. Dysregulation of these events is characteristic of SLE, a systemic autoimmune disease characterized by the appearance of ANAs. In this study, we aimed to investigate the relationship between development of ANAs and their effect on complement activation by nucleic acids. Methods: We used protein array technology to characterize complement activation by murine mAbs and polyclonal antibodies against various forms of nucleic acid. Serum samples from MRL/lpr mice were collected, starting before the onset of the disease till 6 months of age. Binding of IgG and its subclasses to dsDNA, ssDNA, RNA, plasmid DNA and nucleosome complexes was determined, along with C3 fixation. Results: We show that complement C3 binding to various forms of nucleic acid that serve as targets in lupus is absent in normal serum. The addition of dsDNA-specific mAbs to normal serum results in the deposition of complement C3 to nucleic acids. In MRL/lpr mice, IgG antibodies against various nuclear antigens appear with ageing and disease progression. C3 binding to the antigens is somewhat delayed and suggests that accumulation or maturation of pathogenic antibodies is required for inducing C3 binding to ICs containing nucleic acids. Conclusions: C3 deposition on nuclear antigens, therefore, reflects the state of disease progression in this murine model of SLE.

Original languageEnglish
Pages (from-to)2273-2280
Number of pages8
JournalRheumatology
Volume49
Issue number12
DOIs
Publication statusPublished - Dec 2010

Keywords

  • Anti-DNA antibody
  • Autoantibody
  • Complement C3 component
  • Complement activation
  • Lupus

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

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