Immunoglobulin G Fc region (IgG Fc) (IgG Fc)

Pathogenic autoantibodies of the Immunoglobulin G (IgG) class are primary drivers of various autoimmune disorders, where they mistakenly target self-antigens and trigger tissue damage (Source: Ludwig et al., Frontiers in Immunology, 2017). The Fc (Fragment crystallizable) region of these antibodies is a critical structural component that mediates their long circulatory half-life and effector functions. Specifically, the IgG Fc region binds to the neonatal Fc receptor (FcRn), a process that rescues the antibody from lysosomal degradation and recycles it back into the bloodstream (Source: Roopenian & Akilesh, Nature Reviews Immunology, 2007). In patients with autoimmune disease, this mechanism unfortunately maintains high levels of the harmful autoantibodies. Therapeutic strategies targeting the IgG Fc region or its interaction with FcRn aim to disrupt this recycling pathway, thereby accelerating the clearance of pathogenic IgG from the body (Source: Gable et al., American Journal of Health-System Pharmacy, 2022). Drugs such as FcRn antagonists or IgG-cleaving enzymes are designed to reduce total and specific IgG levels rapidly, providing a targeted approach to managing IgG-mediated pathologies like generalized myasthenia gravis (Source: Howard et al., The Lancet Neurology, 2021). This therapeutic modality offers a more specific alternative to traditional plasma exchange or non-selective immunosuppression.

Other names

Pathogenic autoantibodiesIgG Fragment crystallizable regionAutoantibody Fc portionSelf-reactive IgGPathogenic IgG

The primary mechanism of action involves the competitive inhibition of the neonatal Fc receptor (FcRn), which prevents the recycling of IgG molecules and leads to their lysosomal degradation (Source: Roopenian & Akilesh, Nature Reviews Immunology, 2007). Alternatively, enzymatic cleavage of the IgG Fc region by agents like imlifidase removes the effector domain, neutralizing the antibody's ability to trigger downstream inflammatory cascades and accelerating its clearance (Source: Jordan et al., NEJM, 2017).