Pathological autoantibody (Autoantibody)

Pathological autoantibodies are immunoglobulins produced by the immune system that erroneously target and bind to an individual's own proteins, cells, or tissues. Under normal physiological conditions, the immune system maintains self-tolerance; however, in autoimmune states, this tolerance is lost, leading to the production of these self-reactive molecules (StatPearls, 2023). Once bound to their targets, pathological autoantibodies drive disease by triggering inflammatory cascades, activating the complement system, or interfering with essential cellular signaling pathways, such as the neuromuscular junction in myasthenia gravis (PubMed, PMID: 33145167). In therapeutic contexts, these antibodies are treated as targets for elimination or reduction. Modern pharmacological interventions include neonatal Fc receptor (FcRn) inhibitors, which block the recycling of IgG antibodies, thereby reducing the serum concentration of pathogenic IgG (NIH, 2021). Other strategies involve B-cell depletion to stop the source of production or physical removal through apheresis. Because of their central role in the pathogenesis of numerous systemic and organ-specific disorders, measuring and neutralizing pathological autoantibodies is a cornerstone of modern rheumatology, neurology, and dermatology.

Other names

Self-reactive antibodyAuto-reactive antibodyPathogenic autoantibodyHumoral autoantigen-binding protein

Drugs targeting pathological autoantibodies typically work by inhibiting the neonatal Fc receptor (FcRn) to accelerate the degradation of IgG, depleting the B-cells that produce them, or physically removing the antibodies from circulation via therapeutic plasma exchange or immunoadsorption.