Ds. Pisetsky et Cf. Reich, The binding of anti-DNA antibodies to phosphorothioate oligonucleotides ina solid phase immunoassay, MOL IMMUNOL, 35(18), 1998, pp. 1161-1170
Phosphorothioate oligonucleotides (S-oligos) are nucleic acid derivatives t
hat are commonly used as antisense agents. These compounds, similar to bact
erial DNA and CpG oligonucleotides, display a variety of immunological acti
vities in vitro and in vivo. To assess further these activities, the antige
nicity of a series of S-oligos was assessed in the solid phase using anti-D
NA antibodies from sera of patients with systemic lupus erythematosus. By E
LISA, S-oligos bound well to anti-DNA antibodies under the same conditions
as calf thymus DNA antigen. The specificity for anti-DNA was established by
competition assays showing cross-inhibition of binding by DNA and S-oligos
. Reactivity with anti-DNA was observed with S-oligos varying in sequence,
suggesting interaction with a conserved determinant not strictly dependent
on the bases. Furthermore, in comparison with a phosphodiester oligomer of
the same sequence, a phosphorothioate showed dramatically increased activit
y. These findings indicate that structural features associated with the S-o
ligo backbone promote specific binding to anti-DNA antibodies and influence
the size requirement for antigenicity in the solid phase. These observatio
ns thus extend the immunological properties of S-oligos and suggest uses of
these compounds in the diagnosis and treatment of autoimmune disease. (C)
1999 Elsevier Science Ltd. All rights reserved.