Pathogenic circulating autoantibodies (AutoAbs)

Pathogenic circulating autoantibodies are self-reactive immunoglobulins that mistakenly target host tissues, serving as the primary drivers of many autoimmune diseases [4, 10]. These molecules cause pathology through diverse mechanisms, including the direct blockade of cell-surface receptors (e.g., acetylcholine receptors in myasthenia gravis), the constitutive activation of receptors (e.g., TSH receptors in Graves' disease), or the formation of inflammatory immune complexes that damage organs like the kidneys [5, 7]. They also trigger tissue injury by activating the complement cascade and engaging Fc-gamma receptors on myeloid cells [4, 10]. Therapeutic targeting of these autoantibodies has shifted from broad immunosuppression to more specific strategies, such as the use of neonatal Fc receptor (FcRn) inhibitors like efgartigimod, which accelerate the degradation of IgG autoantibodies by blocking their recycling pathway [1, 6, 8]. Other approaches include the physical removal of antibodies via plasmapheresis, neutralization with intravenous immunoglobulin (IVIG), or the depletion of the B-cells and plasma cells responsible for their production [11, 14].

Other names

Self-reactive antibodiesAuto-antibodiesPathogenic immunoglobulinsAutoreactive antibodies

Therapeutic strategies target these molecules through several mechanisms: neonatal Fc receptor (FcRn) inhibitors block the recycling of IgG, leading to accelerated lysosomal degradation [1, 6]; plasmapheresis and immunoadsorption physically remove them from circulation [8, 11]; high-dose IVIG neutralizes their activity and competes for Fc receptor binding [4, 11]; and B-cell or plasma cell depleting agents reduce their production at the source [11, 14].