TY - JOUR

T1 - Dynamic Inverse Relationship Between Cell-Free DNA and Anti-dsDNA Antibodies in Experimental SLE Highlights the Potential for Targeted Immunomodulatory Therapy

AU - Melamud, Mark M.

AU - Ermakov, Evgeny A.

AU - Tolmacheva, Anna S.

AU - Nevinsky, Georgy A.

AU - Buneva, Valentina N.

N1 - This work was supported by the Russian Science Foundation [grant number 23-15-00357]. Dynamic Inverse Relationship Between Cell-Free DNA and Anti-dsDNA Antibodies in Experimental SLE Highlights the Potential for Targeted Immunomodulatory Therapy / M. M. Melamud, E. A. Ermakov, A. S. Tolmacheva, G. A. Nevinsky, V. N. Buneva // Pathophysiology. - 2025. - Т. 32. №3. - № 48. DOI: 10.3390/pathophysiology32030048

PY - 2025/9/16

Y1 - 2025/9/16

N2 - Background/Objectives: 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. Methods: 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. Results: 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, p = 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, p = 0.04). Conclusions: 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.

AB - Background/Objectives: 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. Methods: 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. Results: 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, p = 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, p = 0.04). Conclusions: 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.

KW - SLE mouse model

KW - anti-DNA antibodies

KW - cell-free DNA

KW - pristane

KW - systemic lupus erythematosus

KW - systemic lupus erythematosus

KW - cell-free DNA

KW - anti-DNA antibodies

KW - pristane

KW - SLE mouse model

UR - https://www.mendeley.com/catalogue/04ea421c-d98e-3812-9ca5-e6c5316a22ef/

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105017039093&origin=inward

U2 - 10.3390/pathophysiology32030048

DO - 10.3390/pathophysiology32030048

M3 - Article

C2 - 40981107

VL - 32

JO - Pathophysiology

JF - Pathophysiology

SN - 1873-149X

IS - 3

ER -