Autoantibodies and pathogenic antibodies

Autoantibodies and pathogenic antibodies are immunoglobulins produced by the immune system that inappropriately target an individual's own proteins, cells, or tissues (NIH, 2023). These molecules are the primary drivers of autoimmune diseases, where they cause pathology through various mechanisms, including the activation of the complement cascade, induction of antibody-dependent cellular cytotoxicity (ADCC), or direct interference with receptor signaling and enzyme activity (StatPearls, 2024). In the context of drug development, these antibodies are considered therapeutic targets for removal, neutralization, or suppression of production (Nature Reviews Drug Discovery, 2022). Therapeutic strategies include the use of neonatal Fc receptor (FcRn) inhibitors to accelerate the clearance of pathogenic IgG, B-cell depleting therapies to reduce the population of antibody-secreting cells, and physical removal methods like plasmapheresis (Frontiers in Immunology, 2021). Monitoring the levels of specific autoantibodies often serves as a critical biomarker for disease activity and treatment efficacy across a spectrum of conditions, including systemic lupus erythematosus, rheumatoid arthritis, and various rare neurological disorders (Journal of Clinical Investigation, 2020). By reducing the concentration of these pathogenic molecules, clinicians can achieve significant improvement in patient outcomes and quality of life.

Other names

Auto-reactive antibodiesSelf-reactive antibodiesPathological immunoglobulinsAuto-antibodies

Drugs targeting autoantibodies primarily work by: 1) Inhibiting the neonatal Fc receptor (FcRn) to prevent IgG recycling and promote lysosomal degradation (Nature Reviews Drug Discovery, 2022); 2) Depleting B-cells or plasma cells to halt the production of new antibodies (StatPearls, 2024); 3) Neutralizing circulating antibodies through competitive binding with IVIG; or 4) Inhibiting downstream effector pathways such as the complement system (Frontiers in Immunology, 2021).