Fcγ receptors: structure, function and role as genetic risk factors in SLE

Over 30 years ago, receptors for the Fc region of IgG (FcγR) were implicated in the pathogenesis of systemic lupus erythematosus (SLE). Since those pioneering studies, our knowledge of the structure and function of these FcγRs has increased dramatically. We now know that FcγR contributes to the regulation of acquired immunity and to the regulation of innate immune responses where FcγRs act as specific receptors for innate opsonins (CRP and SAP). Our understanding of the genomic architecture of the genes encoding the FcγR has also witnessed remarkable advances. Numerous functionally relevant single-nucleotide polymorphism (SNP) variants and copy number (CN) variants have been characterized in the FcγR genes. Many of these variants have also been shown to associate with risk to development of SLE and some have been associated with disease progression. This review will provide an overview of the FcγR in relation to SLE, including consideration of the role of genetic variants in FcγR in SLE pathogenesis. The difficulties in assessing genetic variation in these genes will be discussed. To enhance our understanding of the functional roles of these receptors in SLE, future research will need to integrate our knowledge of SNP variants, CN variants and the functional diversity of these receptors.