Synthetic Oligonucleotide Probes for Detection of Autoimmune Antibodies

Abstract

In this review, applications of synthetic oligonucleotide probes in diagnostics and studies of autoimmune antibodies against double-stranded DNA (anti-dsDNA) are described. As outlined herein, synthetic oligonucleotides and monoclonal antibodies provide appealing opportunities to develop standard simple assays for detection of antidsDNAs. Recent examples of anti-dsDNA detection using synthetic nucleic acid antigens include those applying surface plasmon resonance (SPR), antibody microarrays and homogeneous, or all-in-solution, detection with fluorescently-labelled probes. Since sequences of the applied nucleic acid antigens and monoclonal antibodies are known, the major benefit of these assays is the ability for the first time to clearly define the structural factors that govern the formation and stability of anti-dsDNA complexes. This is an essential first step toward understanding immune-complex mediated tissue injury in autoimmune conditions such as systemic lupus erythematosus (SLE) and arthritis, which involve production of pathogenic anti-dsDNAs. Moreover, synthetic nucleic acids and monoclonal antibodies have been demonstrated as key tools for the development of novel nucleic acid sensors for serotyping, along with studies of specificity and avidity of the antibody-dsDNA binding process. Among other antigens, fluorescent oligonucleotides prepared by click chemistry between novel alkyne-modified locked nucleic acid (LNA) strands and a series of fluorescent azides are proved to be very promising tools for efficient homogeneous detection of anti-dsDNAs.