الفهرس 
PathogenesisOnly 14 pages are availabe for public view
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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