However, the overall trends of FcγR expression and decreased CD16 on monocytes and neutrophils are in consonance with data from larger cohorts of adult SLE patients.
The data showed a synergistic effect between the FCGR3B and ADAM3A loci with the presence of deletions in both loci significantly increasing the risk to SLE (5.9-fold) compared to the deletion in the single FCGR3B locus (3.6-fold).
The inflammation intensity in the liver decreased with IgG depletion and the lupus IgG-induced liver inflammation in FcγRIII-deficient mice was comparatively low; while, inflammation was increased in FcγRIIb-deficient mice.
Deletions of FCGR3B have been suggested to increase the risk of inflammatory diseases such as systemic lupus erythematosus and rheumatoid arthritis (RA).
Specifically, among all subsets examined, the percentage of CD16- monocytes and total monocytes was the only one that could discriminate active SLE from quiescent SLE (p = 0.033 and 0.026, respectively).
Susceptibility to systemic lupus erythematosus was associated with the FCGR3B*01 allele, as well as with the FCGR3B*01/*01 and FCGR3B*01/*02 genotypes.
The variable gene copy number of FCGR3B is found to be involved in the impaired clearance of immune complexes, which significantly contribute to the pathogenesis of several autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type-1 diabetes and others.
The results demonstrate that FcγRIIa polymorphism is associated with susceptibility to SLE in Brazilian patients, whereas for FcγRIIIb polymorphism no association was found.
The FCGR3B low copy number genotype was also significantly enriched in SLE patients with ulcer, rash, discoid rash, photosensitivity, ascites, nephritis, complement level depression, and anti-double-stranded DNA antibody positivity compared with control subjects.
Copy number variations of FCGR3B are associated with several immune related diseases such as systemic lupus erythematosus, rheumatoid arthritis and primary Sjögren's syndrome.
The frequency of anti-inflammatory MerTK expressing CD14+CD16+ monocytes decreased in SLE. mMer expression was positively correlated with CD163 expression on CD14+ cells.
We conclude that FCGR3B deletion juxtaposes the 5'-regulatory sequences of FCGR2C with the coding sequence of FCGR2B, creating a chimeric gene that results in an ectopic accumulation of FcγRIIb on NK cells and provides an explanation for SLE risk associated with reduced FCGR3B gene copy number.
Therefore, in this study, the transcriptional responses in peripheral T helper cells (CD4(+)) and monocyte subsets (CD16(-) inflammatory and CD16(+) resident monocytes) isolated from patients with SLE, healthy donors (ND) immunised with the yellow fever vaccine YFV-17Dand untreated controls were compared by global gene expression profiling.It was striking that all of the transcripts that were regulated in response to viral exposure were also found to be differentially regulated in SLE, albeit with markedly lower fold-change values.
We excluded studies using SybrGreen-based genotyping and found strong evidence for association between low (<2) FCGR3B CN and systemic lupus erythematosus [OR = 1.59 (1.32-1.92), P(meta)=9.1 × 10(-7)], but not for rheumatoid arthritis [OR = 1.36 (0.89-2.06), P= 0.15].
Given the genetic overlap between systemic lupus erythematosus and systemic sclerosis (SSc) and the strong evidence for FCGR3B CN in the pathology of SLE, we hypothesised that FCGR3B gene dosage influences susceptibility to SSc.
We report that passive transfer of human SLE sera into mice expressing the uniquely human FcγRIIA and FcγRIIIB on neutrophils induces lupus nephritis and in some cases arthritis only when the mice additionally lack the CD18 integrin, Mac-1.
Deletion of Fcγ receptor IIIB, associated with systemic lupus erythematosus, is a result of independent nonallelic homologous recombination events with a frequency of approximately 0.1%.
The human neutrophil antigen-1 allotypes of FcgammaRIIIB and the role of the receptor in SLE are discussed with regard to the recent determination of copy number variation in FCGR3B and the association of low copy number with SLE.