Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes

Dynamic Expression of Qa-2 during Acute Graft Rejection

Human leukocyte antigen (HLA)-G exhibits immunotolerogenicity and is related to allograft acceptance. Qa-2 is the murine homolog of HLA-G; it has structure and functions similar to those of HLA-G. We investigated the dynamic expression of Qa-2 in skin allografts by immunohistochemistry and on peripheral blood lymphocyte subsets by flow cytometry during the entire process of acute graft rejection (AGR) with a murine skin transplantation model to determine its relationship with the pathological changes of allografts and the influence of immunosuppressive therapy. In grafts without immunosuppressive treatment, Qa-2 did not exhibit obvious changes in syngeneic and allogeneic recipients. In contrast, with immunosuppressant-treated grafts, positive expression of Qa-2 was observed. It remained at high levels in the immunosuppressant-treated syngeneic group; however, it became weakly positive and even negative in infiltrating inflammatory cells as AGR advanced, but it remained strongly positive in other skin tissues throughout the AGR process. Qa-2 expression on CD4+ and CD8+ peripheral blood lymphocyte subsets remained stable at a normal level in the non–immunosuppressant-treated syngeneic group. Immunosuppressive treatment can also significantly upregulate Qa-2. In the allogeneic groups, decreased expression was observed when AGR was at histological grades 1 to 2 (well before gross rejection was observed). Qa-2 was upregulated again after the graft was rejected completely. The results suggest that the increase in Qa-2 may be attributed to the use of immunosuppressive treatments. Moreover, Qa-2 expression decreased significantly with AGR progression, suggesting that it may be a potential marker for predicting AGR, especially in the presence of immunosuppressive agents

Mortality after surgery in Europe: a 7 day cohort study

Background: Clinical outcomes after major surgery are poorly described at the national level. Evidence of heterogeneity between hospitals and health-care systems suggests potential to improve care for patients but this potential remains unconfirmed. The European Surgical Outcomes Study was an international study designed to assess outcomes after non-cardiac surgery in Europe.Methods: We did this 7 day cohort study between April 4 and April 11, 2011. We collected data describing consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery in 498 hospitals across 28 European nations. Patients were followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Secondary outcome measures were duration of hospital stay and admission to critical care. We used χ² and Fisher’s exact tests to compare categorical variables and the t test or the Mann-Whitney U test to compare continuous variables. Significance was set at p<0·05. We constructed multilevel logistic regression models to adjust for the differences in mortality rates between countries.Findings: We included 46 539 patients, of whom 1855 (4%) died before hospital discharge. 3599 (8%) patients were admitted to critical care after surgery with a median length of stay of 1·2 days (IQR 0·9–3·6). 1358 (73%) patients who died were not admitted to critical care at any stage after surgery. Crude mortality rates varied widely between countries (from 1·2% [95% CI 0·0–3·0] for Iceland to 21·5% [16·9–26·2] for Latvia). After adjustment for confounding variables, important differences remained between countries when compared with the UK, the country with the largest dataset (OR range from 0·44 [95% CI 0·19 1·05; p=0·06] for Finland to 6·92 [2·37–20·27; p=0·0004] for Poland).Interpretation: The mortality rate for patients undergoing inpatient non-cardiac surgery was higher than anticipated. Variations in mortality between countries suggest the need for national and international strategies to improve care for this group of patients.Funding: European Society of Intensive Care Medicine, European Society of Anaesthesiology