title: Synthetic oligonucleotide antigens modified with locked nucleic acids detect disease specific antibodies.
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.
authors: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, 5230, Denmark.
authors: Simone V
authors: SV
authors: Samuelsen
authors: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, 5230, Denmark.
authors: Ilia A
authors: IA
authors: Solov'yov
authors: Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.
authors: Imelda M
authors: IM
authors: Balboni
authors: Department of Pediatrics, Program in Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
authors: Elizabeth
authors: E
authors: Mellins
authors: Department of Autoimmunology and Biomarkers, Statens Serum Institute, DK-2300 Copenhagen S, Denmark.|Copenhagen Lupus and Vasculitis Clinic, Centre for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, 2100, Denmark.
authors: Christoffer Tandrup
authors: CT
authors: Nielsen
authors: Department of Autoimmunology and Biomarkers, Statens Serum Institute, DK-2300 Copenhagen S, Denmark.|Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, University of Southern Denmark, DK-5000 Odense C, Denmark.
authors: Niels H H
authors: NH
authors: Heegaard
authors: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, 5230, Denmark.
authors: Kira
authors: K
authors: Astakhova
mesh_terms: D000911:Antibodies, Monoclonal / Q000097:blood / Q000378:metabolism*; D000941:Antigens / Q000737:chemistry* / Q000378:metabolism; D015374:Biosensing Techniques / Q000379:methods*; D004247:DNA / Q000737:chemistry / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D056004:Molecular Dynamics Simulation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D020349:Surface Plasmon Resonance
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D009841:Oligonucleotides; C477371:locked nucleic acid; D004247:DNA