Soluble Human Leukocyte antigen-G Expression Research Articles

Soluble Human Leukocyte Antigen-G Expression in Pregnancy Success and Early Pregnancy Loss in Korle-Bu Teaching Hospital

Introduction: Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility complex (MHC) class Ib antigen characterized by a limited polymorphism. The expression of HLA-G at immune privileged sites and its ability to inhibit the effectors functions of immune cells has set HLA-G as a molecule of immune tolerance. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy. Methods: Soluble HLA-G (sHLA-G) levels were measured using a BioVendor sHLA-G ELISA kit following the manufacturer’s protocol. The study participants include women undergoing spontaneous abortion, non-pregnant women, males and an archive sample of women who had normal vaginal deliveries without any complications and any history of malaria infection from gestation to delivery. Results: Soluble HLA-G levels were higher among women undergoing spontaneous abortion as compared to women who had normal vaginal delivery and non-pregnant women. Soluble HLA-G levels were also higher in second trimester as compared to first trimester in both women who had spontaneous abortions and women who had normal delivery. Conclusion: Although sHLA-G levels were higher among women undergoing spontaneous abortion as compared to non-pregnant women and women who had normal delivery, this may be playing a role in the maintenance of maternal immune tolerance to fetal antigen, since plasma sHLA-G levels increased with increasing trimester in both women who had normal delivery and women undergoing spontaneous abortion.

Plasma soluble human leukocyte antigen-G expression is a potential clinical biomarker in patients with hepatitis B virus infection

The significance of upregulated soluble human leukocyte antigen-G (sHLA-G) expression under various pathologic conditions has been discussed. In this study, we evaluated the potential significance of plasma sHLA-G expression in patients with hepatitis B virus (HBV) infection. The study included 90 acute hepatitis B patients (AHB), 131 chronic hepatitis B patients (CHB), 152 resolved hepatitis B individuals (RHB), and 129 normal controls. sHLA-G were determined using enzyme-linked immunosorbent assay. A receiver operating characteristic (ROC) curve was used to evaluate the feasibility of plasma sHLA-G as a biomarker for distinguishing patients with HBV infection. sHLA-G levels in AHB (median, 193.1 U/mL; p < 0.001), CHB (median, 324.6 U/mL; p < 0.001), and RHB (median, 14.8 U/mL; p = 0.006) patients was much higher than that in normal controls (median, 9.0 U/mL). A significant difference for sHLA-G levels was also observed between patients with HBV infection (AHB vs CHB, AHB vs RHB, and CHB vs RHB; all p < 0.001). The area under the ROC curve for sHLA-G levels was 1.000 (p < 0.001) for AHB, 0.993 (p < 0.001) for CHB, and 0.604 (p = 0.003) for RHB patients versus normal controls, respectively. Data also indicated that the percentage of CD4(+)CD25(+)FoxP3(+) T regulatory cells and HLA-G(+)CD14(+) monocytes was significantly increased in AHB and CHB patients compared with normal controls (all p < 0.001). Our findings indicated that induction of HLA-G expression may play a role in HBV immune evasion and sHLA-G levels could be a useful biomarker in HBV infection.

Up‐regulation of HLA‐G expression in cervical premalignant and malignant lesions

The human leukocyte antigen G (HLA-G) molecule, a non-classical major histocompatibility complex class I antigen, exhibits highly limited tissue distribution and gene variation. Recent studies indicate strong immunoinhibitory properties in tumor cells that may favor their escape from anti-tumor immune responses. However, the role of HLA-G in cervical premalignant and malignant lesions has not been defined clearly. In our study, HLA-G expression was studied in cervical tissue from 119 patients with lesions and 22 normal cervical tissue specimens by immunohistochemistry. HLA-G was expressed in 45% (54/119) of cervical lesion-containing tissues while it was rarely detectable (0/22) in the control specimens (P = 0.000). ROC curve analysis showed that HLA-G has an area under the curve (AUC) of 0.694. Furthermore, we investigated soluble HLA-G expression in the plasma of 172 patients with cervical lesions and 20 healthy controls. Significant increases were also observed in soluble HLA-G levels (median, 191.4 vs 45.18 U/ml, P < 0.001). The relative operating characteristic (ROC) curves for soluble HLA-G (sHLA-G), squamous cell carcinoma (SCC), and carbohydrate antigen 125 (CA125) show an AUC of 0.710, 0.634, and 0.588, respectively. At the cut-off values of 108.20 U/ml for sHLA-G, 1.5 ng/ml for SCC, and 35 U/ml for CA125, the sensitivity was 73.30%, 47.83%, and 44.83%, respectively. The detection of soluble HLA-G in plasma may have significance in the early detection of cervical malignant lesions.

Soluble Human Leukocyte Antigen-G Expression and Glucose Tolerance in Subjects with Different Degrees of Adiposity

Type 2 diabetes mellitus (T2DM) and obesity are characterized by a low-grade inflammation, which might be related to the development of insulin resistance. Human leukocyte antigen-G (HLA-G) shows antiinflammatory and tolerogenic properties, including the modulation of CD8+ T-cell cytotoxicity and regulation of CD4+ T-lymphocyte function. These functions are partially shared with IL-10, whose levels are reduced in insulin-resistant states. The aim was to explore the relationship between HLA-G and the metabolic and inflammatory pattern of obesity or T2DM. Soluble HLA-G, IL-6, and IL-10 were measured and related with metabolic and biochemical parameters in 230 volunteers with normal glucose tolerance, impaired glucose tolerance, or T2DM by oral glucose tolerance test. sHLA-G, detected in 144 subjects (sHLA-G positive), was more frequent in T2DM or impaired glucose tolerance subjects than in normal glucose tolerance (chi(2) =18.6; P < 0.0001), and its plasma levels increased progressively across the classes of glucose tolerance. sHLA-G-positive individuals had higher body mass index, systolic blood pressure, and cholesterol levels; a reduced degree of insulin sensitivity; and almost 2-fold higher levels of IL-6, a cytokine related to insulin sensitivity, whereas IL-10 was similar. In the sHLA-G-positive subgroup, by a multivariate regression model, sHLA-G was significantly related to 2-h glucose, the area under insulin curve, and IL-6 levels (multiple r(2) = 0.14; P < 0.001), independently of age, gender, and body mass index. A frequent expression of sHLA-G, linked to a typical biomarker of insulin resistance like IL-6, seems to characterize subjects with an impaired glucose metabolism.

Graduated Embryo Score and soluble human leukocyte antigen-G expression improve assisted reproductive technology outcomes and suggest a basis for elective single-embryo transfer

To evaluate assisted reproductive technology (ART) outcomes by using Graduated Embryo Score (GES) and soluble human leukocyte antigen-G (sHLA-G) expression to select embryos for transfer on day 3. Prospective cohort. Private practice. Women undergoing fresh ART cycles (n = 209). In vitro fertilization using standard protocols. Embryos scoring GES of > or =70 using were selected for transfer on the basis of sHLA-G expression in the culture media on day 2. Pregnancy, implantation, and multiple-gestation rates. Ongoing gestations increased with the number of embryos expressing sHLA-G (37%, 42%, 58%, and 56% with 0, 1, 2, or 3 sHLA-G(+), respectively). With at least two sHLA-G(+) embryos, ongoing gestation and implantation rates were higher than those with fewer than two sHLA-G(+). Differences were even higher for women aged < or =37 years. With at least two sHLA-G(+) embryos, the odds ratio (95% confidence interval) was 1.59 (1.51-1.68) for ongoing gestation compared with the case of fewer than two sHLA-G(+). Age was the most important predictor of outcome; the odds ratio (95% confidence interval) was 2.07 (1.98-2.16) for ongoing gestation in women aged < or =37 years with at least two sHLA-G(+) embryos, compared with the case of women aged 38-40 years. Day 3 embryo transfer using GES and sHLA-G improves ART outcomes by increasing predictive accuracy. High twin rates suggest that couples with at least two sHLA-G(+) embryos consider elective single-embryo transfer.