Synthetic oligonucleotide antigens modified with locked nucleic acids detect disease specific antibodies

Simone V. Samuelsen, Ilia A. Solov'yov, Imelda M. Balboni, Elizabeth Mellins, Christoffer Tandrup Nielsen, Niels H. H. Heegaard, Kira Astakhova

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Abstract

New techniques to detect and quantify antibodies to nucleic acids would provide a significant advance over current methods, which often lack specificity. We investigate the potential of novel antigens containing locked nucleic acids (LNAs) as targets for antibodies. Particularly, employing molecular dynamics we predict optimal nucleotide composition for targeting DNA-binding antibodies. As a proof of concept, we address a problem of detecting anti-DNA antibodies that are characteristic of systemic lupus erythematosus, a chronic autoimmune disease with multiple manifestations. We test the best oligonucleotide binders in surface plasmon resonance studies to analyze binding and kinetic aspects of interactions between antigens and target DNA. These DNA and LNA/DNA sequences showed improved binding in enzyme-linked immunosorbent assay using human samples of pediatric lupus patients. Our results suggest that the novel method is a promising tool to create antigens for research and point-of-care monitoring of anti-DNA antibodies.
Original languageEnglish
Article number35827
JournalScientific Reports
Volume6
Issue number1
Number of pages12
ISSN2045-2322
DOIs
Publication statusPublished - 2016
Externally publishedYes

Bibliographical note

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© The Author(s) 2016

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