Decidual natural killer cells in recurrent spontaneous abortions

Abstract

Background/Aim. A repeated or habitual miscarriage (PSP) is defined as three or more consecutive losses of pregnancy. In the first three months of pregnancy, habitual miscarriages occur in about 1% of pregnant women, out of which 50% are of an unknown etiology. It is believed that among them, the greatest number is the consequence of an inadequate alloimmune response of a women to the pregnancy. The endocrine and immune systems are in a close interaction during the implantation and maintaining of pregnancy. This communication is the most obvious on endometrium of pregnancy decidua. The aim of the study was to identify the number and the subpopulation distribution of the decidual NK cells in the decidua by using an immunohistochemical method. Methods. The research included a group of 30 women who had had two spontaneous miscarriages consecutively in the first three months of their pregnancy, while the curettage after the third spontaneous abortion was histopathologically and immunohistochemically analyzed. The control group consisted of 20 women without a problematic reproductive anamnesis, who had had their pregnancy terminated for social reasons. The criteria for the eliminating from the research were the diagnosed uterus anomalies, positive screening on thrombophilia, as well as women suffering from diabetes melitus and the ones with the thyroid gland function disorder. Results. The number and the phenotype structure of the uterus NK cells were significantly different between the decidua of a normal pregnancy and that in PSP. In the decidua in PSP, there were much more NK cells with the phenotype of the peripheral circulation CD57 and CD56dim, while in the decidua of the control group the dominant cells were the typical uNK cell subpopulation CD56bright. Conclusion. The above mentioned results show that the disregulation of the immunocompetent cells of the decidua, by creating an inadequate cytokine milieu, is one of the mechanism of rejecting the semiallogeneic blastocyst.Uvod/Cilj. Ponavljani ili habitualni pobacaji (PSP) definisu se kao tri ili vise uzastopnih gubitaka trudnoce. U prvom tromesecju, PSP javljaju se kod oko 1% trudnica, pri cemu su 50% nepoznate etiologije. Najveci broj je verovatno posledica neadekvatnog aloimunog odgovora zene na trudnocu. Endokrini i imunoloski sistemi pokazuju interakciju tokom implatacije i trudnoce. Interakcija je najupadljivija upravo na endometrijumu kod trudnoce - decidui. Cilj rada bio je da se imunohistohemijskom metodom u decidui kod PSP nepoznate etiologije utvrdi broj i subpopulaciona distribucija decidualnih ?natural killer? (NK) celija. Metode. Ispitivanjem je bilo obuhvaceno 30 zena sa dva uzastopna spontana pobacaja u prvom trimestru trudnoce, dok je kiretman kod treceg spontanog abortusa bio histopatoloski i imnunohistohemijski analiziran. Kontrolnu grupu cinilo je 20 zena bez opterecene reproduktivne amaneze, sa prekidom trudnoce iz socijalnih razloga. Kriterijumi za iskljucivanje iz studije bile su dijagnostifikovane anomalije uterusa, pozitivan skrining na trombofilije, dijabetes melitus i poremecaj funkcije stitaste zlezde. Rezultati. Ukupan broj NK celija i NK CD57 bio je znacajno veci u tkivu decidue kod spontanih, nego kod namernih abortusa (p < 0,01), dok se broj NK CD56 nije razlikovao. U decidui kod spontanih prekida trudnoce preovladavale su CD56dim celije, a kod namernih prekida CD56bright celije. Zakljucak. Istrazivanje pokazuje da se broj i fenotipska struktura uterusnih NK celija znacajno razlikuje izmedju decidua kod normalne trudnoce i PSP. U decidui kod PSP preovladjuju NK celije fenotipa periferne cirkulacije CD57 i CD56dim, dok u decidui kontrolne grupe dominiraju tipicne uterusne NK celijske subpopulacije CD56bright. Disregulacija imunokompetentnih celija decidue stvaranjem neadekvatnog citokinskog miljea, jedan je od mehanizama odbacivanja semialogene blastociste.