الفهرس | Only 14 pages are availabe for public view |
Abstract Preeclampsia (PE) , which affects 3-5 percent of all pregnancies, is a primary cause of maternal and newborn death and morbidity. Proteinuria is traditionally diagnosed as PE in women with pregnant hypertension and is associated with greater maternal and neonatal morbidity and death when compared to gestational hypertension alone. PE is responsible for around 50,000 maternal deaths worldwide each year. PE is usually associated with intrauterine growth restriction (IUGR), placental abruption, and the requirement for iatrogenic premature birth, all of which are serious complications. Obesity, previous hypertension, advanced age, and diabetes mellitus are all risk factors for pre-eclampsia. It’s also more common in a woman’s first pregnancy and when she’s expecting twins. The underlying mechanism involves aberrant blood vessel development in the placenta, among other things. Several immunosuppressive factors generated by the placenta are involved in maternal-fetal tolerance during mammalian pregnancy. Exosomes produced from the placenta have recently emerged as novel immunological regulators in the maternal immune tolerance. Exosomes are morphologically characterised membrane nanovesicles that are released from endosomal multivesicular bodies (MVB) after fusion with the plasma membrane. MHC class I chain-related (MIC) proteins A and B, human ligands of the activating NK cell receptor NKG2D (natural killer group 2, member D, have previously been found to be produced by the placenta, sorted to MVB of syncytiotrophoblast, and released by MIC-bearing exosomes. The UL-16 binding proteins (ULBP), the second class of human NKG2D ligands, is likewise produced by the placenta. This expression was not caused by CMV infection in the placenta. ULBP1–5 are formed and maintained on microvesicles/exosomes in the MVB of the syncytiotrophoblast, according to immunoelectron microscopy. We show that exosomes containing NKG2D ligands are released by the human placenta using human placenta explant cultures and several experiments. ULBP1–5 and MIC were found on the surface of isolated placental exosomes, which caused down-regulation of the NKG2D receptor on NK, CD8+, and T cells, resulting in reduced in vitro cytotoxicity without impacting the perforin-mediated lytic pathway. Exosome-mediated release of placental NKG2D ligands provides an alternate route for producing bioactive soluble forms of these ligands. These findings support the idea that the placenta is a unique immunosuppressive organ and that NKG2D ligand-bearing placental exosomes play a role in foetal immunological escape.In current study we aimed to study correlation between ULBP1 and MICA/B gene expression in women with preeclampsia The studied subjects were categorized into the following three groups: Group1:It included 40 patients with mild preeclampsia(preeclampsia classified into mild and severe according to blood pressure and proteinuria) group 2:It included 40patients with severe preeclampsia Group3: It included 40 women age matched healthy subjects served as controls Method: In our study real time PCR assement of ULBP1and MICAlB levels in placental tissue(40mild preeclampsia,40 severe preeclampsia and 40pregnant women of similar ages who served as control) Results: the hallmark finding in this study .is the significant increase in ULBP1 and MICA /B levels in preeclampatic women than control There were insignificant differences between studied groups as regard age , gestational age and as regard birth weight there was significant lower in birth weight among cases group versus control In current study we found that there was significant higher in systolic and diastolic blood pressure In current study we found that there was significant higher in urea ,creatinine, SGPT and SGOT among cases versus control but in Hb and platelet count there was significant lower in cases versus control In current study we found that all cases had edema and 28.8% had 1+ proteinuria , 21.3% had 2+ proteinuria ,18.8% had 3+ proteinuria and 31.3% had 4+ proteinuria, As regard history of diabetes 8.8% of cases had positive history of diabetes , all cases with moderate and severe preeclampsia had odema and as regard proteinuria there was significant higher in cases with 3+ and 4+ proteinuria among cases with severe preeclampsia among moderate preeclamosia. There was no significant differences between cases with moderate or severe preeclampsia as regard history of diabetes In current study we found that there was significant higher in ULPB1 , MICA ,MICB in cases versus control, there was significant higher in ULPB1 , MICA ,MICB between cases with moderate or severe preeclampsia In current study we found that 40 cases were mild preeclampsia and 40 were sever preeclampsia with insignificant differences as regard age and gestational age but as regard birth weight there was significant lower among cases with severe preeclampsia In current study we found that there was significant higher in systolic and diastolic blood pressure in severe preeclampsia versus mild preeclampsia In current study we found that there was significant higher in urea ,creatinine, SGPT and SGOT among severe versus moderate preeclampsia but in Hb and platelet count there was significant lower in severe versus moderate preeclampsia This was the first study that assessed the sensitivity and specificity of ULPB1 , MICA , MICB in differentiate between cases and control and in differentiate between cases with severe and moderate preeclampsia we found that AUC of ULPB1 , MICA , MICB in differentiate between cases and control were 0.945 , 0.910, 0.949 respectively and with cut off >0.86,>1.36,>1.64 respectively , sensitivity 91.25% , 83.75% , 85% respectively , specificity 80%,80% , 92.5% respectively , PPV 90.1% , 89.3% , 95.8% respectively and NPV 82.1% , 71.1% 75.6% respectively In current study we found that AUC of ULPB1 , MICA , MICB in differentiate between cases with severe and moderate preeclampsia were 0.844, 0.840, 0.850 respectively and with cut off >1,>1.95,>5.43 respectively, sensitivity 95% , 87.5% , 75% respectively , specificity 70% ,77.5% , 80 % respectively , PPV 76% , 79.5% , 78.9% respectively and NPV 93.3% , 86.1% 76.2% respectively In current study we found that there was significant positive correlation between ULPB1 and age , systolic and diastolic blood pressure ,urea, creatinine,uric acid, SGOT , SGPT ,and significant negative correlation with birth weight, there was significant positive correlation between MICA and systolic and diastolic blood pressure ,gestational age ,urea, creatinine ,uric acid, SGPT ,and significant negative correlation with birth weight. There was significant positive correlation between MICB and systolic and diastolic blood pressure ,urea, creatinine ,uric acid, SGPT ,and presence of ULPB1, MICA |