Although HLA-A3 and A11 have already been reported to become ligands for KIR3DL2 evidences for relevance of the interaction continues to be missing. brief tail and associate using the immune system receptor tyrosine-based activating theme (ITAM)-including signaling string DAP12 [9] [10] . Therefore the nomenclature of the gene family is dependant on the amount of extracellular domains and how big is the cytoplasmic tail; i.e. KIR3DL three extracellular domains lengthy cytoplasmic tail [11]. research have recommended that HLA-A3 and HLA-A11 are ligands of KIR3DL2 [12] but these relationships look like weak and extremely peptide dependent. Certainly to date only 1 peptide (and variations thereof) continues to be CGS19755 reported to aid A3 and A11 reputation by KIR3DL2. Furthermore the significance of the discussion can be unclear especially in light of the finding that this interaction does not lead to fully functional NK cells in contrast to other inhibitory KIR/ligand pairs [13]. Although polymorphism has been studied in many Brazilian populations [14]-[16] allele diversity has CGS19755 not been well characterized. In addition there is little information about the role of allele polymorphism in diseases. Here we analyzed the influence of alleles in an autoimmune disease cohort from Brazil. Pemphigus foliaceus (PF) is an autoimmune blistering disease of skin characterized by autoantibodies against desmoglein-1 a molecule important for cell adhesion [17]. Many genes including class II have already been reported CGS19755 to affiliate with differential susceptibility to PF [18]-[20]. Activating genes tend to be connected with protection in infectious susceptibility and diseases to autoimmunity [21]. Nevertheless we lately showed that the current presence of larger ratios and amounts of activating genes guard against PF [22]. Pemphigus can DcR2 be endemic not merely in Brazil but also in Tunisia and Colombia as well as the disorder can be sporadically seen all over the world [23] [24]. PF can be tightly related to to environmental elements possibly because of substances within the saliva of hematophagous bugs or even to infectious microorganisms that result in the condition in susceptible people [25] [26]. This particularity of PF may clarify why activating KIR continues to be associated with safety against the advancement of the disease. Allelic polymorphism of inhibitory may bring about functional differences moving the total amount of inhibitory and activating indicators in NK cells. can be extremely polymorphic and within practically all haplotypes [6] [27]. As well as the known truth that people carry this gene KIR3DL2 is highly expressed on NK cells [28]. KIR3DL2 can be therefore a solid applicant for disease association studies as some allotypes could present differential inhibitory effects and affect susceptibility to diseases. Moreover we previously demonstrated that activating protect against PF [22]. CGS19755 Therefore we hypothesized that stronger inhibitory KIR3DL2 allotypes could confer risk to PF. Here we show that the allele and the single nucleotide polymorphism (interaction between KIR3DL2 and HLA-A3 and A11. Moreover we also show that the protective SNP marks KIR3DL2 differential expression levels suggesting the necessity for a threshold of inhibition for the development of PF. 2 Results and Discussion 2.1 increases the susceptibility to PF allelic polymorphism and its effect on disease outcome are not well characterized. presence/absence polymorphism as well as combinations of KIR-HLA have been associated with several infectious and autoimmune diseases [21] [29]. In contrast to other autoimmune diseases in which polymorphism has been associated we have reported that activating genes are protective against PF [22]. Here we hypothesized that different KIR3DL2 allotypes could be greater inhibitory than others what could contribute to shift the balance of activating and inhibitory signals on the NK cell surface. Based on previous results allotypes that show greater inhibition could potentially confer risk to PF. To test this hypothesis we sequenced in patients and controls. The frequencies of all alleles are shown in Supplementary Table S1 and frequencies of the most common alleles are shown in Figure 1. The allele was associated with increased susceptibility to PF for both carrier and allele frequencies in Euro-descendants (OR=2.1 p=0.015; OR=2.04 p=0.007 respectively) (Table 1). A statistically non-significant increase of was seen.