The binding of anti-DNA antibodies to phosphorothioate oligonucleotides in a solid phase immunoassay.

Abstract:

:Phosphorothioate oligonucleotides (S-oligos) are nucleic acid derivatives that are commonly used as antisense agents. These compounds, similar to bacterial DNA and CpG oligonucleotides, display a variety of immunological activities in vitro and in vivo. To assess further these activities, the antigenicity of a series of S-oligos was assessed in the solid phase using anti-DNA antibodies from sera of patients with systemic lupus erythematosus. By ELISA, 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 activity. These findings indicate that structural features associated with the S-oligo backbone promote specific binding to anti-DNA antibodies and influence the size requirement for antigenicity in the solid phase. These observations thus extend the immunological properties of S-oligos and suggest uses of these compounds in the diagnosis and treatment of autoimmune disease.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Pisetsky DS,Reich CF 3rd

doi

10.1016/s0161-5890(98)00108-4

subject

Has Abstract

pub_date

1998-12-01 00:00:00

pages

1161-70

issue

18

eissn

0161-5890

issn

1872-9142

pii

S0161589098001084

journal_volume

35

pub_type

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