Synthetic Nucleic Acid Antigens in Localized Scleroderma.

We investigated the impact of synthetic nucleic acid antigens on the autoantibody profiles in patients with localized scleroderma, an autoimmune skin disease. Anti-DNA antibodies, including double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA), are common among autoimmune diseases, such as systemic lupus erythematosus and localized scleroderma. Based on recent studies, we hypothesized that the sequence of nucleic acid antigens has an impact on the autoimmune reactions in localized scleroderma. To test our hypothesis, we synthesized a panel of DNA and RNA antigens and used them for autoantibody profiling of 70 children with localized scleroderma compared with the healthy controls and patients with pediatric systemic lupus erythematosus (as a disease control). Among the tested antigens, dsD4, which contains the sequence of the human oncogene BRAF, showed a particularly strong presence in localized scleroderma but not systemic lupus erythematosus. Disease activity in patients was significantly associated with dsD4 autoantibody levels. We confirmed this result in vivo by using a bleomycin-induced mouse model of localized scleroderma. When administered intraperitoneally, dsD4 promoted an active polyclonal response in the mouse model. Our study highlights sequence specificity for nucleic acid antigens in localized scleroderma that could potentially lead to developing novel early-stage diagnostic tools.

Cation valence dependence of hydrogen bond and stacking potentials in DNA mesoscopic models.

Monovalent and divalent cations play a crucial role in living cells and for molecular techniques such as PCR. Here we evaluate DNA melting temperatures in magnesium (Mg2+) and magnesium­potassium (Mg2++ K+) buffers with a mesoscopic model that allows us to estimate hydrogen bonds and stacking interaction potentials. The Mg2+ and Mg2++ K+ results are compared to previous calculations for sodium ions (Na+), in terms of equivalent sodium concentration and ionic strength. Morse potentials, related to hydrogen bonding, were found to be essentially constant and unaffected by cation conditions. However, for stacking interactions we find a clear dependence with ionic strength and cation valence. The highest ionic strength variations, for both hydrogen bonds and stacking interactions, was found at the sequence terminals. This suggests that end-to-end interactions in DNA will be strongly dependent on cation valence and ionic strength.