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

Over 30 years ago, receptors for the Fc region of IgG (FcgammaR) were implicated in the pathogenesis of systemic lupus erythematosus (SLE). Since those pioneering studies, our knowledge of the structure and function of these FcgammaRs has increased dramatically. We now know that FcgammaR contributes to the regulation of acquired immunity and to the regulation of innate immune responses where FcgammaRs act as specific receptors for innate opsonins (CRP and SAP). Our understanding of the genomic architecture of the genes encoding the FcgammaR has also witnessed remarkable advances. Numerous functionally relevant single-nucleotide polymorphism (SNP) variants and copy number (CN) variants have been characterized in the FcgammaR 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 FcgammaR in relation to SLE, including consideration of the role of genetic variants in FcgammaR 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.