Autoantibodies to dsDNA cross-react with the arginine-glycine-rich domain of heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2) and promote methylation of hnRNP A2

Rheumatology (Oxford). 2003 Jan;42(1):154-61. doi: 10.1093/rheumatology/keg060.

Abstract

Objective: This study was designed to clarify the internalization of anti-DNA antibodies (anti-DNA) into living cells in the pathogenesis of systemic lupus erythematosus (SLE) using anti-DNA monoclonal antibodies (mAbs).

Methods: Anti-DNA mAbs 9D7, 9D7D2, 9A4, 5E3F5, 12B3H2 and 6E11E3 were prepared by a standard hybridoma procedure to determine the interaction of anti-DNA with proteins in different types of cells.

Results: The anti-DNA mAbs reacted with two protein antigens (35 and 50 kDa) in the cells. The 35-kDa antigen was shown to have 100% homology with hnRNP A2. The arginine-glycine-rich domain in hnRNP A2 was found to be the reaction site, and the methylation of hnRNP A2 by PRMT1 (protein arginine methyltransferase 1) was increased by anti-DNA. Moreover, anti-DNA was demonstrated to bind and internalize into the cytoplasm and nucleus.

Conclusion: Nuclear localizing anti-DNA may cross-react with hnRNP A2 to modulate the inflammatory responses and polarize immune reactions associated with SLE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Antinuclear / immunology*
  • Antibodies, Monoclonal / immunology
  • Antigen-Antibody Reactions*
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Cell Nucleus / immunology
  • Cytoplasm / immunology
  • Epitopes
  • Flow Cytometry
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / immunology*
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism
  • Humans
  • Jurkat Cells
  • Lupus Erythematosus, Systemic / immunology*
  • Methylation
  • Mice
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Protein-Arginine N-Methyltransferases / metabolism
  • Rats
  • Tumor Cells, Cultured

Substances

  • Antibodies, Antinuclear
  • Antibodies, Monoclonal
  • Epitopes
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • hnRNP A2
  • Protein-Arginine N-Methyltransferases