Conjugates or dsDNA linked to human gammaglobulin inhibit anti-dsDNA antibodies in vitro.
Previous studies have shown that both nucleosides and oligonucleotides linked to isologous gammaglobulin suppress anti-nucleic acid antibody production both in vivo and in vitro. The aim of this study was to determine whether one can make a DNA-human gammaglobulin (HGG) conjugate which can inhibit anti-double stranded DNA (dsDNA) antibodies obtained from a heterogeneous population of systemic lupus erythematosus (SLE) sera. To do so, we constructed conjugates of sonicated dsDNA fragments of 100-400 base pairs covalently linked to HGG with varying degrees of substitution of DNA:HGG. An ELISA inhibition assay was used to determine which conjugate best inhibits the binding of anti-dsDNA antibodies. Conjugate 2, prepared with monomeric HGG (150 kD) with a high degree of substitution (3.72 DNA:HGG) inhibited the binding of anti-dsDNA antibodies from 27 of 31 SLE sera. In addition, this conjugate inhibited the spontaneous formation of anti-dsDNA in vitro by cultured lymphoid cells from selected SLE patients. Together, this data suggests that a 'generic' tolerogen may provide an antigen specific therapy for SLE.
Mikael
N
N
Center for Blood Research, Boston, MA 02115.
Boguniewicz
M
M
Manakata
Y
Y
Sasaki
T
T
Borel
H
H
Borel
Y
Y
D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D005719:gamma-Globulins / Q000494:pharmacology*
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D005719:gamma-Globulins; D004247:DNA