Anti-double Stranded DNA Antibodies: Origin, Pathogenicity, and Targeted Therapies

Abstract

Systemic lupus erythematosus (SLE) is characterized by high-titer serological autoantibodies, including antibodies that bind to double-stranded DNA (dsDNA). The origin, specificity, and pathogenicity of anti-dsDNA antibodies have been studied from a wider perspective. These autoantibodies have been suggested to contribute to multiple end-organ injuries, especially to lupus nephritis, in patients with SLE. Moreover, serum levels of anti-DNA antibodies fluctuate with disease activity in patients with SLE. By directly binding to self-antigens or indirectly forming immune complexes, anti-dsDNA antibodies can accumulate in the glomerular and tubular basement membrane. These autoantibodies can also trigger the complement cascade, penetrate into living cells, modulate gene expression, and even induce profibrotic phenotypes of renal cells. In addition, the expression of suppressor of cytokine signaling 1 is reduced by anti-DNA antibodies simultaneously with upregulation of profibrotic genes. Anti-dsDNA antibodies may even participate in the pathogenesis of SLE by catalyzing hydrolysis of certain DNA molecules or peptides in cells. Recently, anti-dsDNA antibodies have been explored in greater depth as a therapeutic target in the management of SLE. A substantial amount of data indicates that blockade of pathogenic anti-dsDNA antibodies can prevent or even reverse organ damage in murine models of SLE. This review focuses on the recent research advances regarding the origin, specificity, classification, and pathogenicity of anti-dsDNA antibodies and highlights the emerging therapies associated with them.

Anti-Citrullinated Protein Antibodies in Patients with Rheumatoid Arthritis: Biological Effects and Mechanisms of Immunopathogenesis

“…Patients receiving such treatment showed an increased ratio of regulatory to effector T cells, a reduction in inflammatory cytokines and a decrease in disease activity 1 month after the procedure [167]. Furthermore, based on the success of anti-double-stranded DNA antibodies targeting peptides in systemic lupus erythematosus [168][169][170], scientists have identified two peptides derived from the fibrinogen α chain capable of disrupting ACPA binding to anti-cyclic citrullinated peptide (CCP2) [171]. Through grafting the citrullinated epitopes into a stable scaffold, the synthetic high-affinity peptide-based scavenger of ACPAs demonstrated superior stability with apparent low nanomolar affinity, which makes in vivo testing possible in the future [172].…”

Immunology of IL-12: An update on functional activities and implications for disease

“…Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by antibodies to double-stranded DNA that can affect various parts of the body including for instance skin, joints, kidneys or nervous system (Wang and Xia, 2019[ 205 ]).…”

Targeted Protein Liposomes-Mediated AChE Gene Therapy for Effective Liver Cancer Treatment

“…Mice bearing SMMC-7721 liver cancer were established as described above and randomly divided into 4 groups (n=6 per group), control, AChE, GL/AChE and Tf-PL/AChE. Mice were injected intravenously with saline (control) or therapeutic agent 50 μg/kg at 10,12,14,16,18,20,22,24, and 26 days after implantation. The anti-tumor e ciency was determined according to the tumor volume using the following formula: larger diameter × (smaller diameter/2) 2 .…”