D-penicillamine- and quinidine-induced antinuclear antibodies in A.SW (H-2s) mice: similarities with autoantibodies in spontaneous and heavy metal-induced autoimmunity

Eur J Immunol. 1994 Mar;24(3):723-30. doi: 10.1002/eji.1830240335.

Abstract

Ten percent of human lupus syndromes occur in patients as a result of treatment with certain medications. H-2s mice can produce autoantibodies following treatment with various drugs or heavy metals and they are a potential animal model of drug-induced lupus. We have examined nine anti-chromatin monoclonal antibodies (mAb) from A.SW mice that had been treated with either D-penicillamine or quinidine, two lupus-inducing drugs in humans. These mAb are specific either for DNA or histone-DNA complexes corresponding to nucleo-specific either for DNA or histone-DNA complexes corresponding to nucleosomes or subnucleosome particles. Only one mAb reacts with an unknown chromatin antigen. The V region sequences of six of these mAb were studied and are notable by several features. As previously observed in spontaneous autoantibodies to DNA or histone-DNA complexes, arginine or asparagine residues are found at critical locations throughout the V regions. Many of these residues, potentially important for binding to DNA or DNA-histone complexes, result either from somatic mutations or atypical VH-D-JH rearrangements. Another significant characteristic is that the VH genes of several D-penicillamine- or quinidine-induced mAb are most similar to those of anti-nucleolar mAb obtained from mercury-injected A.SW mice. The implications of these findings for the pathogenesis of spontaneous or induced autoimmunity are discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Antinuclear / biosynthesis*
  • Antibodies, Antinuclear / genetics
  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / genetics
  • Antibody Specificity
  • Autoimmune Diseases / chemically induced*
  • Base Sequence
  • Female
  • Gene Expression
  • Genes, Immunoglobulin*
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin kappa-Chains / genetics
  • Mice
  • Mice, Inbred A
  • Molecular Sequence Data
  • Mutation
  • Penicillamine / pharmacology*
  • Quinidine / pharmacology*
  • RNA, Messenger / genetics
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid

Substances

  • Antibodies, Antinuclear
  • Antibodies, Monoclonal
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Immunoglobulin kappa-Chains
  • RNA, Messenger
  • Penicillamine
  • Quinidine

Associated data

  • GENBANK/X75391
  • GENBANK/X75392
  • GENBANK/X75393
  • GENBANK/X75394
  • GENBANK/X75395
  • GENBANK/X75396
  • GENBANK/X75397
  • GENBANK/X75398
  • GENBANK/X75399
  • GENBANK/X75400
  • GENBANK/X75401