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

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

doi:10.1038/srep35827

Cited by 10 publications

(49 citation statements)

References 42 publications

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“…In a good agreement with our recent study 9 , CTD showed a high number of false positive results in healthy controls (31%), which points on non-specific interactions.…”

Section: Resultssupporting

confidence: 92%

Complexes of DNA with fluorescent dyes are effective reagents for detection of autoimmune antibodies

Domljanovic

Carstens

Okholm

et al. 2017

Sci Rep

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To date, there are multiple assays developed that detect and quantify antibodies in biofluids. Nevertheless, there is still a lack of simple approaches that specifically detect autoimmune antibodies to double-stranded DNA. Herein we investigate the potential of novel nucleic acid complexes as targets for these antibodies. This is done in a simple, rapid and specific immunofluorescence assay. Specifically, employing 3D nanostructures (DNA origami), we present a new approach in the detection and study of human antibodies to DNA. We demonstrate the detection of anti-DNA antibodies that are characteristic of systemic lupus erythematosus, a chronic autoimmune disease with multiple manifestations. We tested the most potent non-covalent pairs of DNA and fluorescent dyes. Several complexes showed specific recognition of autoimmune antibodies in human samples of lupus patients using a simple one-step immunofluorescence method. This makes the novel assay developed herein a promising tool for research and point-of-care monitoring of anti-DNA antibodies. Using this method, we for the first time experimentally confirm that the disease-specific autoimmune antibodies are sensitive to the 3D structure of nucleic acids and not only to the nucleotide sequence, as was previously thought.

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“…In a good agreement with our recent study 9 , CTD showed a high number of false positive results in healthy controls (31%), which points on non-specific interactions.…”

Section: Resultssupporting

confidence: 92%

Complexes of DNA with fluorescent dyes are effective reagents for detection of autoimmune antibodies

Domljanovic

Carstens

Okholm

et al. 2017

Sci Rep

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“…We have shown the unique specificity and sensitivity of synthetic DNA oligonucleotides containing locked nucleic acids (LNA) for recognition by monoclonal a-dsDNAs 22 . Recently, other investigators explored rationally designed peptoid antigens for SLE diagnostics 23 .…”

Section: Introductionmentioning

confidence: 99%

Autoantibody Profiling in Lupus Patients using Synthetic Nucleic Acids

Klečka

Thybo

Macaubas

et al. 2018

Sci Rep

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Autoantibodies to nuclear components of cells (antinuclear antibodies, ANA), including DNA (a-DNA), are widely used in the diagnosis and subtyping of certain autoimmune diseases, including systemic lupus erythematosus (SLE). Despite clinical use over decades, precise, reproducible measurement of a-DNA titers remains difficult, likely due to the substantial sequence and length heterogeneity of DNA purified from natural sources. We designed and tested a panel of synthetic nucleic acid molecules composed of native deoxyribonucleotide units to measure a-DNA. ELISA assays using these antigens show specificity and reproducibility. Applying the ELISA tests to serological studies of pediatric and adult SLE, we identified novel clinical correlations. We also observed preferential recognition of a specific synthetic antigen by antibodies in SLE sera. We determined the probable basis for this finding using computational analyses, providing valuable structural information for future development of DNA antigens. Synthetic nucleic acid molecules offer the opportunity to standardize assays and to dissect antibody-antigen interactions.

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“…The graphene layers with deposited amino acids were neutralized in water using NaCl by assuming the height of the simulation box equal to 45Å. The protocol was largely adopted from earlier MD simulation on similar systems [17][18][19]. Particle mesh Ewald method was used to treat the long-range electrostatics [20,21] with a cutoff distance of 12Å.…”

Section: Classical Molecular Dynamics Simulationsmentioning

confidence: 99%

Computational analysis of amino acids’ adhesion to the graphene surface

Frederiksen

Solov’yov

2020

Eur. Phys. J. D

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The mechanisms of cellular growth have attracted scientists' attention for a long time, leading to recent efforts in establishing cellular growth on specific functionalized substrates. In order to fully understand the supported cellular growth mechanisms, one needs first to comprehend how individual amino acids interact with the substrate material as cells are known to attach to surfaces through specific proteins designed to improve adhesion. In this study, we have considered graphene as a candidate material for support-assisted cellular growth and simulated the interaction of all 20 naturally occurring amino acids deposited on graphene. Investigations utilized classical molecular dynamics (MD) for amino acids in aqueous solution and in vacuo, in tandem with quantum chemical calculations. The MD simulations were carried out for classical and polarizable CHARMM force fields. The simulations performed with the polarizable force field confirmed that adhesion of amino acids to the graphene surface may be significantly enhanced due to the polarization forces, which was further supported by quantum chemical calculations. The performed analysis thus revealed the role of polarization on amino acids' adhesion to the graphene surface.

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

Cited by 10 publications

References 42 publications

Complexes of DNA with fluorescent dyes are effective reagents for detection of autoimmune antibodies

Complexes of DNA with fluorescent dyes are effective reagents for detection of autoimmune antibodies

Autoantibody Profiling in Lupus Patients using Synthetic Nucleic Acids

Computational analysis of amino acids’ adhesion to the graphene surface

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