Autoantibodies to nuclear antigens: correlation between cytotoxicity and DNA-hydrolyzing activity.
The cytotoxicity of DNA-specific autoantibodies from sera of patients with systemic lupus erythematosis (SLE) and with lymphoproliferative diseases, and from blood of healthy donors was examined on tumor-cell lines L929 and HL-60. DNA-binding IgG fractions from SLE and chronic lymphocytic leukemia (CLL) sera were cytotoxic at concentrations of up to 10(-10) M. No detectable changes in cell viability were observed after incubation with antibodies devoid of DNA-binding activity and DNA-specific antibodies isolated from blood of healthy donors and patients with T-cell lymphoma, B-cell lymphosarcoma, and acute B-cell leukemia. There was good correlation between the cytotoxic activity and DNA-hydrolyzing activity of anti-DNA antibodies. The cytotoxic effect of DNA-binding antibodies presumably was complement-independent, because it was attributed only to the Fab fragment. The cytotoxic effect was completely inhibited by preincubation with double-stranded DNA (dsDNA). Both the cytotoxic effect and the DNA-hydrolyzing activity of anti-DNA antibodies were significantly increased in the antibody fraction that displayed cross-reactivity with nuclear matrix proteins. Possible mechanisms for the formation and pathogenicity of cytotoxic anti-DNA antibodies are discussed in this article.
Kozyr
A V
AV
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow.
Kolesnikov
A V
AV
Zelenova
N A
NA
Sashchenko
L P
LP
Mikhalap
S V
SV
Bulina
M E
ME
Ignatova
A N
AN
Favorov
P V
PV
Gabibov
A G
AG
D000974:Antibodies, Antinuclear / Q000097:blood / Q000378:metabolism*; D017151:Antibodies, Catalytic / Q000097:blood / Q000378:metabolism*; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000276:immunology* / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D006868:Hydrolysis; D007128:Immunoglobulin Fragments / Q000097:blood / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000276:immunology; D009685:Nuclear Envelope / Q000276:immunology; D015530:Nuclear Matrix / Q000276:immunology; D014407:Tumor Cells, Cultured
D000974:Antibodies, Antinuclear; D017151:Antibodies, Catalytic; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D004247:DNA