Spencer Diane M, Svenungsson Elisabet, Gunnarsson Iva, Caricchio Roberto, Pisetsky David S
Division of Rheumatology and Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Clin Immunol. 2023 Oct;255:109763. doi: 10.1016/j.clim.2023.109763. Epub 2023 Sep 9.
To explore the antibody response to Z-DNA, a DNA conformation with a zig-zag structure, blood of patients with systemic lupus erythematosus (SLE) and otherwise healthy individuals (NHS) were assayed by ELISA using brominated poly(dGdC), a synthetic Z-DNA antigen. These studies showed that SLE patients commonly express antibodies to Z-DNA; NHS also had binding in this assay. In SLE blood, levels of antibodies to Z-DNA were related to those to B-DNA using calf thymus DNA as a source of B-DNA; cross-reactivity was demonstrated by adsorption experiments using DNA cellulose. As shown by dissociation assays, antibody binding of SLE anti-Z-DNA is sensitive to the effects of ionic strength, suggesting electrostatic binding. Since Z-DNA structure can be found in bacterial DNA as well as bacterial biofilms, these findings suggest that, in SLE, anti-DNA antibody responses can result from stimulation by DNA of bacterial origin, with cross-reactivity leading to autoreactivity.
为了探究针对Z-DNA（一种具有锯齿状结构的DNA构象）的抗体反应，利用溴化聚（dGdC）（一种合成的Z-DNA抗原）通过酶联免疫吸附测定法（ELISA）检测了系统性红斑狼疮（SLE）患者和健康个体（NHS）的血液。这些研究表明，SLE患者通常表达针对Z-DNA的抗体；在该检测中NHS也有结合反应。在SLE患者血液中，以小牛胸腺DNA作为B-DNA来源时，针对Z-DNA的抗体水平与针对B-DNA的抗体水平相关；使用DNA纤维素的吸附实验证明了交叉反应性。解离分析表明，SLE抗Z-DNA抗体的结合对离子强度的影响敏感，提示存在静电结合。由于Z-DNA结构可在细菌DNA以及细菌生物膜中发现，这些发现表明，在SLE中，抗DNA抗体反应可能由细菌来源的DNA刺激引起，交叉反应性导致自身反应性。
