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

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 (<i>p</i> < 0.04) than the subgroup with low activity, which had a shorter duration of the disease (<i>p</i> = 0.03) and was more often characterized by a subacute rather than a non-chronic course of the disease (<i>p</i> = 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.