The Therapeutic Strategies for SLE by Targeting Anti-dsDNA Antibodies

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by diverse serological autoantibodies. Anti-dsDNA antibodies are involved in multiple organ damage, especially the kidney, skin, and central nervous system. Anti-dsDNA antibodies play a pivotal role in SLE, and researchers have developed therapeutic strategies targeting these antibodies. Approaches to reduce anti-dsDNA antibodies via B cell targeted biologics against B cell surface antigens, B cell survival factors, or Bruton’s tyrosine kinase have effectively eliminated B cells. However, their non-specific depletion hampers normal immune system functioning and limits the therapeutic benefits. Thus, scientists have attempted anti-dsDNA antibodies or lupus-specific strategies, such as the immature dendritic cell vaccine and immunoadsorption. Recently, synthetic mimic peptides (hCDR1, pCONs, DWEYS, FISLE-412, and ALW) that directly block anti-dsDNA autoantibodies have attracted attention, which could ameliorate lupus, decrease the serological autoantibody titer, reduce the deposition of renal autoantibodies, and improve pathological performance. These potent small peptide molecules are well tolerated, non-toxic, and non-immunogenic, which have demonstrated a benign safety profile and are expected to be hopeful candidates for SLE management. In this review, we clarify the role of anti-dsDNA antibodies in SLE, mainly focus on the current strategies targeting anti-dsDNA antibodies, and discuss their potential clinical value.

Anti-dsDNA Is Associated with Favorable Prognosis in Myasthenia Gravis: A Retrospective Study

“…Another unexpected finding was that anti-dsDNA was associated with MG-ADL score reduction. This finding was contrary to findings in previous studies wherein anti-dsDNA was involved in multiple organ injury in SLE, especially in the kidney, skin, and central nervous system [56]. However, the results of these previous studies may have been due to different pathogeneses.…”

FGL1-LAG3 axis impairs IL-10-Producing regulatory T cells associated with Systemic lupus erythematosus disease activity

“…B cell abnormalities are involved in SLE disease progression through the production of autoantibodies such as anti-dsDNA antibodies [ 6 , 44 ]. Here, we found that the anti-dsDNA antibody titer was negatively correlated with serum IL-10 level ( Fig.…”

Effects of DNA Immunoadsorption Combined with Medication on Immune Function and Renal Function in Patients with Systemic Lupus Erythematosus

“…DNA immunoadsorption therapy uses antigens or other substances with specific physicochemical affinity as ligands, which are combined with the carrier and connected to the adsorption column. Specific adsorption is used to eliminate endogenous pathogenic factors in patients' blood, so as to exert the effects of purifying blood, eliminating immune complexes and immunoglobulins in patients with SLE, alleviating target organ damage, and achieving the effects of targeted therapy for SLE [ 16 , 17 ].…”