D-penicillamine- and quinidine-induced antinuclear antibodies in A.SW (H-2s) mice: similarities with autoantibodies in spontaneous and heavy metal-induced autoimmunity.
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.
Monestier
M
M
Garden State Cancer Center, Newark, NJ.
Novick
K E
KE
Losman
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000235:genetics; D000918:Antibody Specificity; D001327:Autoimmune Diseases / Q000139:chemically induced*; D001483:Base Sequence; D005260:Female; D015870:Gene Expression; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D051379:Mice; D008805:Mice, Inbred A; D008969:Molecular Sequence Data; D009154:Mutation; D010396:Penicillamine / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D012333:RNA, Messenger; D010396:Penicillamine; D011802:Quinidine