IntroductionBehçet's disease is a chronic systemic inflammatory disease that remains incompletely understood. Herein, we perform the first genome-wide association study in Behçet's disease.MethodsUsing DNA pooling technology and the Affymetrix 500K arrays, we identified possible candidate gene associations with Behçet's disease in a cohort of 152 Behçet's disease patients and 172 healthy ethnically matched controls. Genetic loci that were identified in the pooling study were genotyped in patients and controls using TaqMan genotyping technology.ResultsWe identified genetic associations between Behçet's disease and single-nucleotide polymorphisms (SNPs) in KIAA1529, CPVL, LOC100129342, UBASH3B, and UBAC2 (odds ratio = 2.04, 2.26, 1.84, 1.71, and 1.61, respectively; P value = 4.2 × 10-5, 1.0 × 10-4, 3.0 × 10-4, 1.5 × 10-3, and 5.8 × 10-3, respectively). Among the associated SNPs, the Behçet's disease-risk allele in rs2061634 leads to substitution of serine to cysteine at amino acid position 995 (S995C) in the KIAA1529 protein.ConclusionsUsing an unbiased whole-genome genetic association approach, we identified novel candidate genetic loci that are associated with increased susceptibility for Behçet's disease. These findings will help to better understand the pathogenesis of Behçet's disease and identify novel targets for therapeutic intervention.

CD40 ligand (CD40LG), encoded on the X chromosome, has been reported to be overexpressed on lupus Tcells. Herein, we investigated the effect of DNA demethylation on Tcell CD40LG expression and the production of IgG by autologous B cells in lupus. We found normal human T cells transfected with CD40LG induced autologous B cell activation and plasma cell differentiation. Both female lupus CD4+ T cells and demethylating agents treated CD4+ T cells overexpressed CD40LG mRNA. Further, lupus T cells from both genders or demethylated CD4+ T cells from healthy women overstimulated autologous B cells, and this could be reversed with anti-CD40LG Ab in only females. We demonstrated that female lupus CD4+ T cells and demethylated CD4+ T cells express high level of CD40LG and overstimulate B cells to produce IgG. This is due to DNA demethylation and thereby reactivation of the inactive X chromosome in female.

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