FcRn Inhibition in Autoantibody-Mediated Autoimmune Diseases: From Broad Immunosuppression to Precision IgG Modulation

Abstract

The therapeutic landscape of autoimmune disease is undergoing a conceptual transition. For decades, treatment has relied predominantly on broad immunosuppression, which has substantially reduced morbidity and mortality but remains limited by systemic toxicity and impaired host defence. Advances in molecular immunology have enabled mechanism-based therapies that target pathogenic pathways more selectively while preserving much of normal immune function. Inhibition of the neonatal Fc receptor (FcRn) is a leading example of this approach in IgG-mediated autoimmunity. By interrupting FcRn-dependent IgG recycling, FcRn antagonists accelerate the degradation of circulating IgG, including pathogenic autoanti-bodies, without directly suppressing lymphocyte production or broadly inhibiting cytokine networks. This review summarises the biological basis of FcRn-mediated IgG homeostasis, the rationale for therapeutic FcRn blockade, and its clinical implications across autoantibody-mediated autoimmune diseases. FcRn inhibition exemplifies the transition from empirical immunosuppression to precision immunomodulation and provides a platform for selectively modifying the persistence of disease-causing antibodies.