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580 Blighted Ovum: Roles of Human Leukocyte Antigen-E and Natural ORIGINAL ARTICLE Bali Medical Journal (Bali Med J) 2017, Volume 6, Number 2: 381-385 P-ISSN.2089-1180, E-ISSN.2302-2914 Blighted ovum: Roles of human leukocyte antigen-E ORIGINAL ARTICLE and natural killer cells CrossMark Doi: http://dx.doi.org/10.15562/bmj.v6i2.580 Sri Sulistyowati,* Febri Rahadian, Supriyadi Hari Respati, Soetrisno Published by DiscoverSys ABSTRACT Volume No.: 6 Background: The failure of premature conception product is a specific uman Leukocyte Antigen-E and Natural Killer Cell cells in trophoblast problem for pregnant women. Blighted Ovum occurred in 37.5% of early of both groups were examined with immunohistochemical methods pregnancy failure. About 15% of Blighted Ovum is caused by disorders and statistical analysis that was done by t-test. Issue: 2 of the immune system. Human Leukocyte Antigen-E and Natural Killer Results: The mean of expression of Human Leukocyte Antigen-E Cell are supposed to be the main factors of this pathomechanism. in the group of Blighted Ovum are 75.15±6:30, normal pregnancy Objective: To determine the expression of Human Leukocyte are 83.13±11:26, p-value=0:02 (P <0.05). The mean of expression Antigen-E and Natural Killer Cell cells in the Blighted Ovum and normal of NK cells in the group of a normal pregnancy is 79.72±6.63, while First page No.: 381 pregnancy. the mean of expression of NK cells in Blighted Ovum is 93.88±14.08, Methods: Observational analytic with cross sectional approach. p-value=0.00 (P<0.05). Thirty-two samples were divided into two groups: 16 samples of Conclusion: The expression of HLA-E was lower, and NK cells were P-ISSN.2089-1180 Blighted Ovum group and 16 samples of normal pregnancy group. higher in Blighted Ovum when compared with normal pregnancy. Keywords: Human Leukocyte Antigen-E, NK cell, Blighted Ovum E-ISSN.2302-2914 Cite This Article: Sulistyowati, S., Rahadian, F., Respati, S.H., Soetrisno. 2017. Blighted ovum: roles of human leukocyte antigen-E and natural killer cells. Bali Medical Journal 6(2): 381-385. DOI:10.15562/bmj.v6i2.580 Department of Obstetric and INTRODUCTION Gynecology, Faculty of Medicine, Universitas Sebelas Maret / Blighted Ovum also knew as an anembryonic Pregnancy is a biological sample that is Dr. Moewardi General Hospital pregnancy where there are pockets of intrauterine semi-allogeneic which may be rejected by the Surakarta pregnancies without their fetus. Blighted Ovum is maternal immune system. The fetus is consid- a form of failure of pregnancy that is common and ered a foreign body by the mother that can be occurs in the first semester.1 Failure of the premature destroyed, so it must have the ability to evade conception product is a specific problem for many the maternal immune system.4 The fetus that is pregnant women and also constitutes an obstetric semi-allogeneic consisting of trophoblast cells at complication. Criteria of premature conception the stage of conception. During the first trimester product failure are spontaneous abortion, anembry- of pregnancy, the placenta develops into a villous onic pregnancy/Blighted Ovum, and fetal death.2 form with trophoblast cell types which has different Blighted Ovum often occur at the start or very functions.5 Trophoblast is a factor that is allegedly early in the pregnancy so not all cases can be essential to this phenomenon because it unfolds in diagnosed with Blighted Ovum which makes the the maternal–fetal interface, where there is a direct number of an event difficult to know for certain. contact with the maternal immune system.6 Approximately about 20% of all pregnancies end in The issue that is important in pregnancy is how miscarriage/abortion, and 80% of them occur at the the fetoplacental relationship avoids the rejection age less than 12 weeks of pregnancy and one-third of the maternal immune system, although the fetus occur before the age of 8 weeks which is Blighted was bonded during pregnancy. Sir Peter Medawar, *Correspondence to: Sri Sulistyowati, Ovum. The incidence of the general failure of prema- an immunology expert, suggests that a fetus that Department of Obstetric and ture conception product was 2.8%; Blighted Ovum is semi-allogenic can survive because of their rela- Gynecology, Faculty of Medicine, Universitas Sebelas Maret / is about 37.5% of premature conception product tionships with immune system and emphasis on Dr. Moewardi General Hospital failure that occurs at 10–13 weeks of pregnancy.2 maternal lymphocytes with the fetus.7,8 Defects Surakarta The causes of Blighted Ovum that frequently in the bond between the fetus and the mother, in [email protected] mentioned are chromosomal abnormalities (dupli- this case, is trophoblast. Associated with various cations or deletions), genetic abnormalities (muta- complications of pregnancy such as preeclampsia, Received: 2017-03-08 tions of genes), lack of good quality of the ovum intrauterine growth retardation, and failure of Accepted: 2017-05-5 and sperm, maternal age factor, endocrine, and conception product (Blighted Ovum, recurrent Published: 2017-05-8 immunologist factors.3 miscarriage, and IUFD).9 Open access: www.balimedicaljournal.org and ojs.unud.ac.id/index.php/bmj 381 ORIGINAL ARTICLE Nowadays, Human Leukocyte Antigen (HLA) The sample size was determined based on the molecule is suspected to play an important role in formula of Murti (2010) in which each group was maintaining the product of conception.10 16 samples. Thirteen (?) is the inclusion criteria for Human Leukocyte Antigen (HLA)-E is Blighted Ovum: a non-classical HLA class I, which plays an important role to regulate cytokine secretion as 1. Maternal age 20–35 years. controller of trophoblast invasion and regulate 2. The transvaginal ultrasound examination to immune tolerance locally in the placenta. Human visualize the intrauterine gestational sac, which Leukocyte Antigen-E is predominantly expressed is without an embryo or fetal pole structure on in extravillous of trophoblast in the placenta and gestational age of 8 weeks with a gestational the formation of the hematopoietic system that is sac size of 2.5 cm, and the normal pregnancy derived from the extraembryonic yolk sac. Human are: aged 37–40 weeks, a single fetus in the Leukocyte Antigen-E can protect trophoblasts intrauterine was found with no complications from maternal–fetal immune intolerance and allow during pregnancy and childbirth. trophoblast cells to invade the uterus. Human Leukocyte Antigen-E plays an important role in All subjects were willing to participate in immune tolerance during pregnancy.11 research. Exclusion criteria are mothers with Appropriate HLA-E expression in the tropho- diabetes mellitus, kidney disease, heart disease, blast is necessary to help trophoblasts invading liver disease, chronic hypertension, infectious maternal decidua and vascular system, so there is an diseases, smoking, and fetuses with major congen- increase in uterine perfusion that is needed during ital abnormalities. Both groups were examined for pregnancy. However, if the HLA-E was reduced or the expression of HLA-E and NK cells in extravil- not being expressed, the trophoblast cells capability lous trophoblast where HLA-E was expressed and will be reduced and prevented from invading the decidua NK cells accumulated in the vicinity. uterus because it was perceived as non-self which The expressions of HLA-E and NK cells in the has properties as antigens that trigger the formation immunohistochemical examination is indicated of antibodies in the mother. These antibodies bind with a bluish tint for weak positive, golden yellow to antigens, and immunological reaction occurs for moderate positive, and brown for strong posi- that stimulates activation of proinflammatory cyto- tive on the trophoblast. Trophoblast cell number kines, activated T-cells, and natural killer cells (NK) was calculated based on the intensity of the expres- that will attack trophoblast cell itself, resulting in sion which is then created with the percentage of the failure of the conception product.10 overall cell numbers. The obtained percentage was Natural Killer cells in pregnant women have the then converted into numbers and calculated dual function of NK cells through a receptor, which according to the formula of the histological score inhibits CD94/ NKG2A and activating via the CD94 (HS). The ratings of ( meaning look of?) HLA-E and receptor/ NKG2C. The imbalance of these receptors NK cells expressed as HS was done based on the can lead to failure in pregnancy, Blighted Ovum formula: HS=(PK × IK) + (PS × IS) + (PL × IL) + as the example. Natural killer cells are activated (PN × IN) through CD94 receptor / NKG2C will produce cyto- kines that attack the trophoblasts and ruin it so that Formula’s explanation: the embryo will experience rejection in uterus.12 P=Percentage K=Strong N=Negative This study aims to determine the expression I=Intensity L=Weak S=Moderate of HLA-E and NK cells in trophoblast of Blighted Ovum and normal pregnancy which is expected to Histology score of HLA-E and NK cells (percent- be a predictor so that the incidence of the Blighted age of cells: 0–25%=negative; 26–50%=weak posi- Ovum can be lowered. tive; 51–75%=moderate positive; 76–100%=strong positive). Histology score of HLA-E and NK cells METHODS (qualitative meaning: 0.00–3.75=negative; 3.76– 7.50=weak positive; 7.51–11.25=moderate positive; This study is an analytic observational with a 11.26–15, 00=strong positive.14 cross-sectional study; it is carried out at the Reagents used for the expression of HLA-E Obstetrics and Gynecology Hospital Dr. Moewardi using HLA-E antibody by Santacruz Biotechnology Surakarta and hospital networks. Examination of brand and reagents used for the expression of the expression of HLA-E and NK cells with immu- NK cells is a rabbit polyclonal antibody, an anti- nohistochemistry method that was performed at KIR2DL1 bs-2419R BIOSs, Inc that is used to see the Laboratory of Pathology, Faculty of Medicine, the expression of NK cell receptors, that is KIR.
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