Anti-FCGR2B monoclonal antibody, clone DDH47 [R-PE]

The aim of this study was to investigate the role of Fc gamma RIIB gene in susceptibility to systemic lupus erythematosus (SLE) using family-based association methods. In total, 119 patients with SLE from 95 nuclear families, aged from 14 to 78 years, who met the American College of Rheumatology (ACR) 1997 criteria, were recruited, as were 316 family members of these patients. A family-based association analysis was used to explore the relationship between gene polymorphism and SLE. We studied three single-nucleotide polymorphisms (SNPs, rs10917661, rs5017567, and rs1050499) encoding non-synonymous substitution in the Fc gamma RIIB gene with respect to genetic susceptibility to SLE in collection of 435 subjects from 95 nuclear families. We performed the genotyping using PCR-restriction fragment length polymorphism method. Among 119 SLE patients, the frequencies of Fc gamma RIIB Gln/Gln,Gln/Ter and Ter/Ter genotypes were 12.7, 60.7 and 26.6%. Univariate (single-marker) family-based association tests (FBATs) demonstrated that variant alleles at a SNP, rs10917661, in exon 2 of Fc gamma RIIB gene were significantly associated with genetic susceptibility to SLE in additive model (exon 2, Z = 3.444, P = 0.00057). transmission/disequilibrium test (TDT) and sibship disequilibuium test (SDT) analysis showed an excess of the alleles of 50Ter from heterozygous parents to affected offspring (chi(2) = 10.88, P = 0.0013). However, the rs5017567 and rs1050499 SNPs were not found in Chinese population. Our findings provide strong evidence suggesting that a Fc gamma RIIB-Gln50Ter loci might be the susceptible factor of SLE in Chinese population.

Although large-scale studies established many susceptibility genes to systemic lupus erythematosus (SLE), effect of each gene is not sufficiently large to be used alone to identify individuals with strong genetic predisposition. In this study, we analyzed the cumulative number of risk alleles at eight established susceptibility loci, HLA-DRB1, IRF5, STAT4, BLK, TNFAIP3, TNIP1, FCGR2B and TNFSF13, in 282 Japanese female SLE and 222 healthy female controls. The average number of risk alleles was significantly increased in SLE (8.07 +/- 1.60) than healthy controls (7.02 +/- 1.64) (P=1.63 x 10(-12)). Significant gene-gene interaction was not detected. When the subjects carrying seven risk alleles were used as a reference, the odds ratio (OR) for individuals carrying 10 and 11-13 risk alleles were 4.17 (95% confidence interval (CI) 1.89-9.19, P=0.0002) and 8.77 (95% CI 1.92-40.0, P=0.0016), respectively. In contrast, subjects with <= 4 risk alleles were significantly decreased in SLE (OR 0.15, CI 0.03-0.67, P=0.007). The proportion of the patients with neurologic disorder was significantly increased in those carrying >= 10 risk alleles than those with <10 (OR 2.30, CI 1.09-4.83, P=0.025). This study suggested that the cumulative number of risk alleles may efficiently distinguish groups with high and low genetic predisposition to SLE and its severe manifestation. Journal of Human Genetics (2011) 56, 503-507; doi: 10.1038/jhg.2011.49; published online 12 May 2011