TY - JOUR

T1 - Catalytic IgG Antibodies Hydrolyze DNA, Histones, and HMGB1 in Systemic Lupus Erythematosus

AU - Melamud, Mark M

AU - Ermakov, Evgeny A

AU - Tolmacheva, Anna S

AU - Kostrikina, Irina A

AU - Sizikov, Alexey E

AU - Nevinsky, Georgy A

AU - Buneva, Valentina N

N1 - This work was partly supported by the Russian Science Foundation [grant number 23-15-00357] (part of the work on the analysis of DNase, HMGB1-, and histone-hydrolyzing activity of IgG) and the Russian state-funded project for ICBFM SB RAS [grant number 125012300658-9] (part of the work on the analysis of catalase-like activity of IgG). Catalytic IgG Antibodies Hydrolyze DNA, Histones, and HMGB1 in Systemic Lupus Erythematosus / M. M. Melamud, E. A. Ermakov, A. S. Tolmacheva, I. A. Kostrikina, A. E. Sizikov, G. A. Nevinsky, V. N. Buneva // International Journal of Molecular Sciences. – 2025. – Vol. 26, No. 19. – DOI 10.3390/ijms26199635

PY - 2025/10/2

Y1 - 2025/10/2

N2 - Antinuclear antibodies, especially anti-DNA antibodies, are known to be a hallmark of systemic lupus erythematosus (SLE) and represent a diverse pool of autoantibodies with different origins, antigenic properties, and physicochemical features. Antibodies with catalytic properties have been found among the antibody repertoire in SLE, but the specific features and clinical associations of such antibodies have not been sufficiently studied. This study showed that chromatographically purified IgG from the serum of SLE patients effectively hydrolyzed DNA and DNA-associated proteins such as histones and high-mobility group box 1 (HMGB1) compared to healthy individuals. Remarkably, the level of hydrolysis of DNA and DNA-associated proteins was closely correlated. At the same time, these antibodies did not hydrolyze the control protein, tumor necrosis factor-α (TNFα), which does not possess DNA-binding properties. IgG DNase activity levels varied significantly, so patients were divided into high- and low-activity subgroups using the DBSCAN algorithm, with the difference between median values being greater than 49 times. The subgroup with high IgG DNase activity was characterized by an increase in anti-DNA antibodies (p < 0.04) than the subgroup with low activity, which had a shorter duration of the disease (p = 0.03) and was more often characterized by a subacute rather than a non-chronic course of the disease (p = 0.048). High catalase-like activity of IgG was also detected in SLE. Thus, the antibody pool in SLE contains not only high-affinity antinuclear autoantibodies but also catalytic antibodies capable of hydrolyzing DNA and DNA-associated proteins. These findings expand our understanding of the heterogeneity of the repertoire of catalytic autoantibodies among SLE patients.

AB - Antinuclear antibodies, especially anti-DNA antibodies, are known to be a hallmark of systemic lupus erythematosus (SLE) and represent a diverse pool of autoantibodies with different origins, antigenic properties, and physicochemical features. Antibodies with catalytic properties have been found among the antibody repertoire in SLE, but the specific features and clinical associations of such antibodies have not been sufficiently studied. This study showed that chromatographically purified IgG from the serum of SLE patients effectively hydrolyzed DNA and DNA-associated proteins such as histones and high-mobility group box 1 (HMGB1) compared to healthy individuals. Remarkably, the level of hydrolysis of DNA and DNA-associated proteins was closely correlated. At the same time, these antibodies did not hydrolyze the control protein, tumor necrosis factor-α (TNFα), which does not possess DNA-binding properties. IgG DNase activity levels varied significantly, so patients were divided into high- and low-activity subgroups using the DBSCAN algorithm, with the difference between median values being greater than 49 times. The subgroup with high IgG DNase activity was characterized by an increase in anti-DNA antibodies (p < 0.04) than the subgroup with low activity, which had a shorter duration of the disease (p = 0.03) and was more often characterized by a subacute rather than a non-chronic course of the disease (p = 0.048). High catalase-like activity of IgG was also detected in SLE. Thus, the antibody pool in SLE contains not only high-affinity antinuclear autoantibodies but also catalytic antibodies capable of hydrolyzing DNA and DNA-associated proteins. These findings expand our understanding of the heterogeneity of the repertoire of catalytic autoantibodies among SLE patients.

KW - Lupus Erythematosus, Systemic/immunology

KW - Humans

KW - Immunoglobulin G/immunology

KW - DNA/metabolism

KW - HMGB1 Protein/metabolism

KW - Female

KW - Histones/metabolism

KW - Adult

KW - Antibodies, Catalytic/immunology

KW - Male

KW - Middle Aged

KW - Antibodies, Antinuclear/immunology

KW - Hydrolysis

UR - https://pubmed.ncbi.nlm.nih.gov/41096902/

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105018892683&origin=inward

U2 - 10.3390/ijms26199635

DO - 10.3390/ijms26199635

M3 - Article

C2 - 41096902

VL - 26

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 19

ER -