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Lupus
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Conjugates or dsDNA Linked to Human Gammaglobulin Inhibit Anti-dsDNA Antibodies In Vitro

Nagy Mikael

Center for Blood Research, 800 Huntington Avenue, Boston, MA 02115, Department of Medicine, The Faulkner Hospital, Boston, MA

Mark Boguniewicz

Center for Blood Research, 800 Huntington Avenue, Boston, MA 02115, Division of Immunology, The Children's Hospital, Boston, MA

Yasuhiko Manakata

Second Department of Internal Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, Japan 980

Takashi Sasaki, M.D.

Division of Immunology, The Children's Hospital, Boston, MA

Halina Borel

Center for Blood Research, 800 Huntington Avenue, Boston, MA 02115

Yves Borel

Center for Blood Research, 800 Huntington Avenue, Boston, MA 02115, Division of Immunology, The Children's Hospital, Boston, MA

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 eruthematosus (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.

Key Words: Systemic lupus erythematosus • Anti-dsDNA antibody • dsDNA-human gammaglobulin conjugates

Lupus, Vol. 3, No. 3, 173-179 (1994)
DOI: 10.1177/096120339400300308
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