Human Leucocyte Antigen G and Murine Qa-2 Are Critical for Myeloid Derived Suppressor Cell Expansion and Activation and for Successful Pregnancy Outcome

During pregnancy, maternal immune system has to balance tightly between protection against pathogens and tolerance towards a semi-allogeneic organism. Dysfunction of this immune adaptation can lead to severe complications such as pregnancy loss, preeclampsia or fetal growth restriction. In the present study we analyzed the impact of the murine MHC class Ib molecule Qa-2 on pregnancy outcome in vivo. We demonstrate that lack of Qa-2 led to intrauterine growth restriction and increased abortion rates especially in late pregnancy accompanied by a disturbed trophoblast invasion and altered spiral artery remodeling as well as protein aggregation in trophoblast cells indicating a preeclampsia-like phenotype. Furthermore, lack of Qa-2 caused imbalanced immunological adaptation to pregnancy with altered immune cell and especially T-cell homeostasis, reduced Treg numbers and decreased accumulation and functional activation of myeloid-derived suppressor cells. Lastly, we show that application of sHLA-G reduced abortion rates in Qa-2 deficient mice by inducing MDSC. Our results highlight the importance of an interaction between HLA-G and MDSC for pregnancy success and the therapeutic potential of HLA-G for treatment of immunological pregnancy complications.

Risk Factors of Pregnancy Outcome in Patients with Pulmonary Hypertension

OBJECTIVE: The purpose of this study is to explore the factors affecting the pregnancy outcome of patients with pulmonary hypertension, and to design a digital model predicting the pregnancy outcome of patients and judge whether patients have the conditions to continue pregnancy. METHODS: The clinical data of patients with pregnancy complicated with pulmonary hypertension hospitalized in Guangdong Provincial People's Hospital from January 1, 2014 to December 31, 2020 were retrospectively analyzed. The severity of pulmonary hypertension, the structural and functional indexes measured by echocardiography were compared, and the effects on maternal and neonatal outcomes were analyzed. RESULTS: A total of 158 patients met the inclusion and exclusion criteria. The results showed that tricuspid regurgitation velocity (P<0.001), right ventricular diameter (P<0.05), right atrial diameter (P<0.05), pulmonary artery diameter (P<0.001) and cardiac function classification (P<0.001) were risk factors for maternal outcomes; Tricuspid regurgitation velocity (P<0.001) and structural changes of right heart were risk factors for neonatal outcomes. By multivariate logistic regression analysis, tricuspid regurgitation velocity (P<0.001), cardiac function (P<0.05) and superior inferior diameter of right atrium (P<0.05) were significant risk factors for maternal outcomes, while tricuspid regurgitation velocity (P<0.001) and superior inferior diameter of right atrium (P<0.05) were significant risk factors for neonatal outcomes. Using significant risk factors, a risk score system was established to predict the pregnancy outcome. CONCLUSION: in this study, we analyzed the clinical data of patients with pregnancy complicated with pulmonary hypertension in our hospital in recent years, and found that the changes of right heart structure (the acceleration of tricuspid regurgitation velocity, and the increase of right atrium, right ventricular diameter, right ventricular outflow tract anteroposterior diameter and main pulmonary artery diameter), are influencing factors of pregnancy outcomes in patients with pulmonary hypertension. In addition, we preliminarily designed a risk score through multi factor analysis, which is helpful to predict the possible outcome of puerperium and neonatal outcomes of patients, and to provide some reference for clinicians and patients to make decisions on whether to continue pregnancy in clinical practice.