Differential expression of immune checkpoints (OX40/OX40L and PD-1/PD-L1) in decidua of unexplained recurrent spontaneous abortion women.

In this study, we aimed to investigate the expression of OX40, OX40L, PD-1 and PD-L1 in patients with unexplained recurrent spontaneous abortion (URSA) compared to normal pregnancies (NP). A total of 50 patients who were diagnosed with URSA and 41 NP were recruited to this study. Real-time polymerase chain reaction (RT-PCR) was used to determine the expression of OX40, OX40L, PD-1 and PD-L1 in decidual tissues; Immunohistochemistry (IHC) was conducted to characterize the distribution of the involved genes in decidual tissues; Double immunofluorescence staining was used to prove the localization of the involved genes in decidual tissues. The concentrations of OX40L and PD-L1 in plasma were measured with enzyme-linked immunosorbent assay (ELISA). The expression of OX40L in the decidua of URSA patients was significantly increased compared to that in the NP group, while the expression of PD-L1 in the URSA group was decreased compared to that in the NP group. Both proteins are localized in the decidual stroma as analyzed by double immunofluorescence staining. The staining results were confirmed at the mRNA level of decidual tissues, while the mRNA level of peripheral blood showed no significant difference. In conclusion, the results suggest that decidual stromal cells may promote the interaction with OX40 on T cells by upregulating the expression of OX40L and reduce the interaction with PD-1 on T cells by downregulating the expression of PD-L1 in URSA patients, which may interfere with the immune tolerance of the maternal-fetal interface, leading to poor pregnancy outcomes.

Distinct changes of in BTLA, ICOS, PD-1, and TIGIT expression on peripheral blood and decidual CD8+ T cells in women with unexplained recurrent spontaneous abortion†.

The two-way communication between the mother and the fetus is accomplished by immune cells. CD8+ T cells of normal pregnant (NP) women express progesterone receptor (PR). Binding of PR to progesterone (P) and the production of progesterone-induced blocking factor (PIBF) can aid immune escape, which is an important factor in the maternal immune response. We detected the proportion of CD8+ T cells and the expression of the surface costimulatory molecules BTLA, TIGIT, ICOS, and PD-1 in peripheral blood and decidual tissues of women with unexplained recurrent spontaneous abortion (URSA) and in NP women. All patients were at 8 -10 weeks of gestation. The results showed that there was no change in the proportions of CD8+ T cells in peripheral blood and decidual tissues of URSA patients compared to those of NP women. In peripheral blood, compared with the NP group, the URSA group showed decreased expression of BTLA + CD8+ T cells and the difference was statistically significant, but there was no difference between the groups in terms of TIGIT + CD8+, PD-1 + CD8+, and ICOS + CD8+ T cells. There was no change in the levels of TIGIT + CD8+, PD-1 + CD8+, ICOS + CD8+, and BTLA + CD8+ T cells in decidual tissue. These data confirm that the number of CD8+ T cells in peripheral blood and decidual tissue is not the main factor leading to the pathogenesis of URSA, and other immune cells may play an important role in URSA, but this hypothesis needs further exploration and research.

Diagnostic value of 18F-FDG PET/MRI in recurrent pelvis malignancies of female patients: a systematic review and meta-analysis.

The aim of this study was to assess the diagnostic performance of fluorine-18-fluorodeoxyglucose (F-FDG) PET/MRI for suspected recurrence of pelvis malignancies of female patients using a meta-analysis. We performed a systematical literature search for relevant studies in PubMed, Cochrane Library, Google Scholar, and several Chinese databases. Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the quality of all included studies. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated per patient and per lesion. Summary receiver operating characteristic curves were also constructed. All procedures involving human participants in this study were performed in conformity with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments. Finally, seven articles comprising 257 patients and 695 lesions were included in this meta-analysis. On patient-based analysis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of F-FDG PET/MRI in detecting recurrence of pelvis malignancies were 0.96 [95% confidence interval (CI): 0.93-0.99], 0.95 (95% CI: 0.87-0.99), 9.85 (95% CI: 4.62-21.00), 0.07 (95% CI: 0.04-0.13), and 201.41 (95% CI: 62.89-645.03), respectively. On lesion-based analysis, the corresponding estimates were 0.99 (95% CI: 0.97-1.00), 0.94 (95% CI: 0.89-0.97), 17.11 (95% CI: 4.46-65.60), 0.02 (95% CI: 0.01-0.05), and 1125.24 (95% CI: 211.46-5987.79), respectively. The results of our meta-analysis indicate that F-FDG PET/MRI has excellent diagnostic performance in restaging female patients with suspected recurrence of gynecological pelvic malignancies.