Low affinity immunoglobulin gamma Fc receptor IIa (CD32a) (CD32a)

Low affinity immunoglobulin gamma Fc receptor IIa (CD32a), encoded by the FCGR2A gene, is a cell surface glycoprotein that binds the Fc portion of IgG antibodies to initiate various immune responses (UniProt P12318). On plasmacytoid dendritic cells (pDCs), CD32a is the sole Fc gamma receptor expressed and plays a pivotal role in the pathogenesis of autoimmune diseases like Systemic Lupus Erythematosus (SLE) (PubMed: 15548671). It mediates the internalization of immune complexes containing self-nucleic acids, which then activate endosomal Toll-like receptors 7 and 9, leading to the massive production of Type I interferons (PubMed: 21355063). This pDC-IFN axis is a major driver of chronic inflammation and tissue damage in lupus. Consequently, CD32a is a significant therapeutic target for inhibiting the uptake of pathogenic immune complexes. However, a major challenge in targeting CD32a is its expression on platelets, where receptor cross-linking can trigger platelet activation and lead to serious side effects such as thrombocytopenia or thrombosis. Current research focuses on developing selective inhibitors or Fc-engineered antibodies that can modulate pDC activity while avoiding adverse effects on platelets.

Other names

Fc gamma receptor IIaFCGR2ACD32FCG2FCGR2IGFR2CDw32

Blockade of immune complex internalization to prevent endosomal TLR7/9 activation and subsequent Type I Interferon production.