FCGR2A

Fc gamma receptor IIA (FCGR2A), also known as CD32a, is a transmembrane glycoprotein encoded by the FCGR2A gene. It binds to the Fc region of immunoglobulin G (IgG) immune complexes, mediating critical immune responses such as phagocytosis, antibody-dependent cellular cytotoxicity (ADCC), and cytokine release. Structurally, FCGR2A contains an immunoreceptor tyrosine-based activation motif (ITAM) that recruits Syk kinase upon ligand binding, activating downstream pathways including MAPK, NF-κB, and PI3K/AKT. These pathways regulate inflammation, cell survival, and antigen presentation. FCGR2A polymorphisms, particularly H131R (histidine to arginine substitution), influence receptor affinity for IgG subclasses, impacting disease susceptibility and therapeutic responses.
Dysregulation of FCGR2A is implicated in autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis) and infectious diseases. In SLE, impaired clearance of immune complexes due to FCGR2A variants exacerbates inflammation. Conversely, enhanced FCGR2A signaling may contribute to thrombotic disorders like heparin-induced thrombocytopenia. Therapeutic strategies targeting FCGR2A include monoclonal antibodies (e.g., rituximab) optimized for Fc-FcγR interactions to boost efficacy. Fc-engineered biologics (e.g., obinutuzumab) and small-molecule inhibitors modulating ITAM signaling are under investigation. Recent clinical trials explore FCGR2A as a biomarker for predicting responses to IVIg therapy and checkpoint inhibitors in cancer immunotherapy.