Melamud Mark M, Ermakov Evgeny A, Tolmacheva Anna S, Nevinsky Georgy A, Buneva Valentina N
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia.
Pathophysiology. 2025 Sep 16;32(3):48. doi: 10.3390/pathophysiology32030048.
: The pathognomonic feature of systemic lupus erythematosus (SLE) is the formation of antibodies to double-stranded DNA (anti-dsDNA Abs). Cell-free DNA (cfDNA) has been suggested as one of the antigens for the generation of anti-dsDNA Abs, but the temporal changes in these biomarkers are not clear. In this study, the association of dynamic changes in total cfDNA and anti-dsDNA Abs levels in blood plasma during disease progression in a murine model of pristane-induced SLE was examined. : The experimental group consisted of 12 BALB/c pristane-immunized mice; the control group included 8 PBS-treated mice. Blood samples were collected six times during the 38-week study (2 weeks before and 8, 14, 22, 28, and 36 weeks after immunization). Total cfDNA and anti-dsDNA Abs levels were determined at each time point. : Pristane-immunized mice showed a significant increase in the concentration of anti-dsDNA Abs. A 14-week delay in the formation of anti-dsDNA Abs was observed after an increase in the concentration of cfDNA in the experimental and control groups. Anti-dsDNA Abs and total cfDNA levels did not correlate at specific time points, but the change in cfDNA concentration from week 14 to week 28 was inversely correlated with the change in the anti-dsDNA Abs level over the same time period (R = -0.71, = 0.009), i.e., the more the anti-dsDNA Abs level increased, the more the cfDNA concentration decreased. A direct correlation was shown between the increase in body weight of pristane-immunized mice and the increase in total cfDNA concentration in the blood from week 0 to week 14 (R = 0.6, = 0.04). : These findings demonstrate the dynamic nature of cfDNA and anti-dsDNA Abs levels and reciprocal dynamics of these markers in a pristane-induced mouse model of SLE.
系统性红斑狼疮（SLE）的特征性表现是抗双链DNA抗体（抗dsDNA抗体）的形成。游离DNA（cfDNA）被认为是抗dsDNA抗体产生的抗原之一，但这些生物标志物的时间变化尚不清楚。在本研究中，检测了在 pristane 诱导的 SLE 小鼠模型疾病进展过程中血浆中总 cfDNA 和抗 dsDNA 抗体水平的动态变化之间的关联。实验组由 12 只经 pristane 免疫的 BALB/c 小鼠组成；对照组包括 8 只经 PBS 处理的小鼠。在为期 38 周的研究期间（免疫前 2 周以及免疫后 8、14、22、28 和 36 周）采集了 6 次血样。在每个时间点测定总 cfDNA 和抗 dsDNA 抗体水平。经 pristane 免疫的小鼠抗 dsDNA 抗体浓度显著增加。在实验组和对照组中，cfDNA 浓度增加后观察到抗 dsDNA 抗体形成延迟 14 周。抗 dsDNA 抗体和总 cfDNA 水平在特定时间点不相关，但从第 14 周到第 28 周 cfDNA 浓度的变化与同一时期抗 dsDNA 抗体水平的变化呈负相关（R = -0.71，P = 0.009），即抗 dsDNA 抗体水平增加越多，cfDNA 浓度下降越多。从第 0 周到第 14 周，经 pristane 免疫的小鼠体重增加与血液中总 cfDNA 浓度增加之间呈正相关（R = 0.6，P = 0.04）。这些发现证明了在 pristane 诱导的 SLE 小鼠模型中 cfDNA 和抗 dsDNA 抗体水平的动态性质以及这些标志物的相互动态关系。
