Autoantibody Profiling in Lupus Patients using Synthetic Nucleic Acids

Martin Klecka, Christina Thybo, Claudia Macaubas, Ilia Solov'yov, Julia Simard, Imelda Maria Balboni, Emily Fox, Anne Voss, Elizabeth D. Mellins, Kira Astakhova
Scientific Reports
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\øf 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.