Synthetic Nucleic Acid Antigens in Localized Scleroderma

• Published in: International journal of molecular sciences 2023-12, Vol.24 (24), p.17507
• Main Authors: Khatri, Sangita, Bustos, Adrian H, Jørgensen, Christian Damsgaard, Torok, Kathryn S, Gjerdrum, Lise-Mette Rahbek, Astakhova, Kira
• Format: Article
• Language: English
• Subjects: Acids; Animals; Antibodies; Antigens; Apoptosis; Autoantibodies - genetics; Autoimmune Diseases; autoimmunity; Child; Collagen; Cytokines; Disease; DNA; DNA, Single-Stranded; dsD4; Generalized linear models; Genes; Humans; Immunoglobulins; Ligands; localized scleroderma; Lupus Erythematosus, Systemic; Lymphocytes; Mice; Pathogenesis; Scleroderma; Scleroderma, Localized; synthetic nucleic acid antigens; Tumor necrosis factor-TNF
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms242417507

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 , 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.