The Secretions Ability Of SHLA-G Controlled By The Genetic Polymorphism Is Associated With Psoriasis Vulgaris

Psoriasis vulgaris is considered as a T cell-mediated autoimmune disease that affects1-3%of the population worldwide, and is responsible for significant morbidity. The disease is characterized by intense hyperproliferation of epidermal keratinocytes and T-cell infiltration. Genetic epidemiological studies have demonstrated a significant genetic susceptibility to psoriasis. In view of the HLA-G immune regulating function, previous studies provide evidence that HLA-G may be associated with development of psoriasis.Human leukocyte antigen (HLA)-G is a nonclassical HLA class Ib gene located on the short arm of chromosome6in the major histocompatibility complex. It resembles the classical HLA class Ia genes in structure but has a very limited polymorphism, and HLA-G transcripts are alternatively spliced into seven different isoforms, whereas encode both membrane-bound (HLA-G1,-G2,-and-G4) and soluble (HLA-G5,-G6and-G7) isoforms. HLA-G may have a role in the suppression of immune responses and contribute to long-term immune escape or tolerance. The existing research shows that, in some pathological conditions, HLA-G expression will be raised or expression is reduced, its possible mechanism is not clear. But research shows that HLA-G gene polymorphism may affect its expression, such as pre-eclampsia, habitual spontaneous abortion, autoimmune diseases, asthma and so on. HLA-G expression is abnormal in relation to polymorphism of HLA-G gene3’untranslated region (3’UTR) and5’upstream regulatory region (5’URR). HLA-G may play a role as immunosuppressive molecules, in psoriasis occurrence, development and prognosis, but the specific mechanism is not clear. In this study, we first established a measure method for the secretions ability of sHLA-G to peripheral blood mononuclear cells (PBMCs) in vitro, namely PBMCs from healthy individuals (n=100) and psoriasis vulgaris patients (n=98) were activated with dexamethasone(1μg/ml) in48h, and the secretion ability of sHLA-G was investigated by specific immunoenzymatic assay. We recruited100control subjects and98psoriasis vulgaris patients for this study. We have focused only on association of the HLA-G14-bp insertion/deletion, HLA-G*0105N polymorphism and HLA-G gene+3142sites of single nucleotide polymorphisms with psoriasis vulgaris, differences of the concentration in plasma sHLA-G and the secretion ability of sHLA-G antigens in dexamethasone-stimulated PBMC cultures. How to influences sHLA-G concentration of plasma and the secretion ability of sHLA-G in activated PBMCs of HLA-G polymorphism. Through multivariate factorial variance analysis to clarify the association of HLA-G polymorphism with psoriasis vulgaris and its possible mechanism.The main content includes.1. Association of the HLA-G14-bp insertion/deletion and HLA-G*0105N polymorphism with psoriasis vulgarisOur findings showed a significant difference of the HLA-G14bp genotype, HLA-G*0105N allele frequency among patients as compared with controls (p<0.05). Our data suggest that the HLA-G14bp allele and HLA-G*0105N allele are probably the risk factor for psoriasis.We also found that HLA-G gene+3142C/G ploylmorphism may not be a genetic risk of psoriasis in Chinese population.2. The plasma sHLA-G levels and the secretion ability of sHLA-G antigens from PBMCs following dexamethasone activation were at a significantly lower level in the psoriatic group than the normal individualsThis case-control study enrolled100control subjects and98psoriasis vulgaris patients. Peripheral blood mononuclear cells (PBMCs) from healthy individuals (n=100) and psoriasis vulgaris patients (n=98) were activated with dexamethasone(1μg/ml), and the levels of sHLA-G in plasma and the secretion ability of sHLA-G was investigated by specific immunoenzymatic assay. Results showed that the significantly lower plasma levels of sHLA-G was found in psoriatic group compared to controls. The values of plasma sHLA-G was15.27±1.02ng/ml vs21.94±1.472ng/ml respectively (p<0.001). The secretion ability of sHLA-G antigens was significantly lower in the psoriatic group compared to the control group with the value of6.103ng/ml vs7.65ng/ml (P<0.001). The results indicate that the secretion ability of sHLA-G may be associated with development of psoriasis.3. HLA-G14bp and HLA-G*0105N genotypes influence sHLA-G concentration of plasma and the production levels of sHLA-G in activated PBMCsNo dramatic difference for plasma sHLA-G concentration was observed between the groups with+14bp/+14bp and with+14bp/-14bp and-14bp/-14bp genotypes (P>0.05). The plasma sHLA-G concentration of the C/-genotype was12.85ng/ml while that of the C/C genotype was20.44ng/ml. The difference was significant (P=0.0006). HLA-G14bp genotypes are associated with the secretion ability of sHLA-G in activated PBMCs. Data showed that sHLA-G expression with the genotype-14bp/-14bp was dramatically lower than that with the genotypes+14bp/-14bp (P=0.0114) and-14bp/-14bp (P<0.0001). The secretion ability of sHLA-G for the C/-genotype was4.624ng/ml while that of the C/C genotype was7.627ng/ml. The difference was significant (P<0.0001). This indicates a genetic dominant effect for the C/-genotype in reducing protein production. HLA-G+3142C>G genotypes could not significantly affect the plasma and secretions ability of sHLA-G. Comparison was performed with Mann-Whitney t test.4. The secretion ability of sHLA-G controlled by the genetic polymorphism is associated with psoriasis vulgarisWith multivariate factorial variance analysis, we found that HLA-G14bp and*0105N genotype distribution may influence the secretion ability of sHLA-G antigens following dexamethasone activation, hence leading to low healthy levels, it is possible importance in psoriasis vulgaris.