Title T regulacijski limfociti i prirodnoubojičke stanice u vilitisu nepoznate etiologije posteljica iz trudnoća kompliciranih preeklampsijom
Title (english) T regulatory lymphocytes and NK cells in the placentae with villitis of unknown etiology from the pregnancies complicated with preeclampsia
Author Sandra Benzon
Mentor Ivana Kuzmić Prusac (mentor)
Committee member Janoš Terzić (predsjednik povjerenstva)
Committee member Tomislav Strinić (član povjerenstva)
Committee member Marina Kos (član povjerenstva)
Granter University of Split School of Medicine Split
Defense date and country 2018, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Pathology
Universal decimal classification (UDC ) 616 - Pathology. Clinical medicine
Abstract Cilj: Istražiti i odrediti broj i vrstu T limfocitnog infiltrata kao i broj T reg limfocita u žarištima VUE posteljica trudnoća kompliciranih PE i usporediti ih s brojem u posteljicama s VUE bez PE. Istražiti i odrediti broj T reg limfocita i NK stanica u decidui bazalis posteljica s VUE s i bez PE i kontrolne skupine urednih trudnoća te ih međusobno usporediti. Istražiti stupanj i žarišta VUE u posteljicama trudnoća kompliciranih PE i usporediti ih sa stupnjem i žarištima VUE u posteljicama trudnoća bez PE.
Materijali i metode: Ispitivane skupine čine 27 posteljica s VUE iz trudnoća kompliciranih PE i 27 posteljica s nalazom VUE iz trudnoća bez PE, te 20 posteljica iz urednih trudnoća. Klinička dijagnoza PE postavljena je prema strogim kriterijima arterijske hipertenzije i proteinurije, a dijagnoza VUE prema prisutnosti limfohistiocitnog infiltrata koji je zahvaćao različitu proporciju posteljičnih resica. Broj i vrsta T limfocitnog infiltrata u žarištima VUE kao i broj T reg i NK stanica u decidui bazalis određeni su imunohistokemijskom uporabom specifičnih antitijela: CD3, CD4, CD25, FOXP3, CD8, CD45LCA, CD68 i CD56. Određivani su i broj žarišta i stupanj VUE.
Rezultati: Nije bilo statistički značajne razlike u smislu broja žarišta i stupnja VUE između skupine s VUE i PE i VUE bez PE. Nije nađena statistički značajna razlika u smislu pariteta, majčinih godina, porođajne mase djece, dužine djece i gestacijske dobi između navedenih skupina, ali je pronađena statistički značajna razlika u porođajnoj masi i gestacijskoj dobi između skupina VUE s i bez PE i kontrolne skupine. Analiza broja T limfocita između skupina s VUE s i bez PE ukazala je na statistički značajnu razliku u ukupnom broju CD4+ limfocita, broju resica infiltriranih s CD4+ limfocitima te omjeru CD4+/CD8+ u skupini s VUE i PE u odnosu na skupinu s VUE bez PE. Nije uočena statistički značajna razlika ukupnog broja i vrste upalnih stanica, niti broja zahvaćenih resica ispitivanih posteljica infiltriranih s CD3, CD8, CD25, FOXP3, CD45LCA i CD68. Analiza T reg limfocita i NK stanica u decidui u posteljicama s VUE s i bez PE te urednih trudnoća ukazala je na statistički značajne razlike u broju CD4+ limfocita između skupina s VUE s i bez PE, te s VUE i PE i kontrole. Nije bilo statistički značajne razlike između skupine s VUE bez PE i kontrole. CD25+ i FOXP3+ bili su negativni. Nismo dokazali statistički značajnu razliku u broju NK stanica između ispitivanih skupina.
Zaključak: T reg limfociti koji iskazuju markere CD4+CD25+FOXP3+, a koji su analizirani u smislu prisutnosti i upliva u žarištima VUE istraživanih posteljica, kao i decidui, pronađeni su pojedinačno i oskudno i bez statistički značajne razlike između ispitivanih skupina. Prirodnoubojičke stanice koje su CD56+, a koje smo analizirali u decidui ispitivanih posteljica nisu se pokazale značajnim ni u jednoj skupini. Žarišta vilitisa posteljica s VUE iz trudnoća kompliciranih PE imaju statistički značajnije veći broj CD4 + limfocita, kao i CD4+/CD8+ omjer nego posteljice s VUE bez PE. Slijedeće istraživanje trebalo bi napraviti na većem uzorku posteljica s VUE i PE, uz analizu cjelokupne subpopulacije CD4+ limfocita, te paralelnu analizu subpopulacije CD4+ limfocita iz periferne krvi istih trudnica, a koji vjerovatno pridonose upalnom odgovoru i simptomima PE. Fiziologija imune interakcije između fetusa i majke za vrijeme trudnoće je još uvijek neistraženo područje koje sve više zaokuplja interes istraživača. Upravo razumijevanje imunološke interakcije za vrijeme normalne trudnoće moglo bi pripomoći istraživanju poremećaja povezanih sa trudnoćom kao što je PE.
Abstract (english) Objective: To compare immunohistochemical expression of different T type lymphocytes as well as T reg lymphocytes in foci of VUE in placentae from pregnancies complicated with PE and in foci of VUE in placentae without PE. To compare immunohistochemical expression of T reg lymphocytes and NK cells in the basal decidua, in placentae with VUE from pregnancies with and without PE and from normal pregnancies. To compare grade and number of foci between VUE in placentae from pregnancies complicated with PE and in placentae from pregnancies without PE.
Material and methods: Fiftyfour placentae were collected from pregnancies who had villitis of unknown etiology with [N=27] and without [N=27] preeclampsia and twenty [N=20] from normal pregnancies. Clinical diagnosis of PE was made according to the strict criteria of hypertension and proteinuria, and diagnosis of VUE according to the presence of lymphohistiocytic infiltrate affecting varying proportions of the villous tree of the placenta. Immunohistochemistry for the number and type of T cell inflammatory infiltrate in VUE foci as well as T reg and NK cells in basal decidua was performed on formalin fixed and paraffin-embedded sections by use of the CD3, CD4, FOXP3, CD25, CD8, CD45, CD56 and CD68 antibodies. Cytomorphological characteristics of examined placentas were determined by the number of foci and grade of VUE.
Results: There was no statistical difference in terms of foci and grade of VUE between VUE with and without PE. Also, there was no statistical difference in terms of parity, maternal age, birth weight, birth length and gestational age, but there was a statistical difference in terms of birth weight and gestational age between VUE with and without PE and control group. There was statistically significant difference in total CD4+ lymphocytes count, number of villi infiltrate with CD4+ lymphocytes and CD4+/CD8+ ratio between VUE with and without PE. No statistically significant difference of the total number and type of inflammatory cells and number of villi infiltrated with CD3, CD8, CD25, FOXP3, CD45 and CD68 between the study groups was detected. Analysis of T reg and NK cells infiltrate in the basal decidua among all three investigated groups revealed statistically significant difference in total CD4+ lymphocytes count between group with VUE with and without PE and with VUE with PE and control group. There was no statistically significant difference between group with VUE without PE and control group. CD25+ i FOXP3+ were negative. No statistically significant difference of the total number of decidual CD56 cells in basal decidua between the study groups was noticed.
Conclusion: T reg lymphocytes expressing the CD4+, CD25+ and FOXP3+ markers were analysed for their presence and influx in VUE foci in the placentae, and were detected individually and rarely, without statistically significant between-group difference, also in decidua. Natural killer cells which were analysed in decidua were detected also individually and rarely without statistically significant between group difference. This study results revealed statistically significantly larger CD4+ T lymphocyte population and CD4+/CD8+ ratio in placentae with VUE with PE compared to VUE without PE. Future studies should include a greater sample of VUE and PE and focus on analysis of the overall CD4+ lymphocyte subpopulation and concurrent analysis of CD4+ lymphocyte subpopulation from peripheral blood collected from the same pregnant women, as these cells probably contribute to the inflammatory response and symptoms of PE, while also being relevant for proper understanding of these intriguing inflammatory lesions of human placenta. The physiology of the immune interaction between the fetus and the mother during pregnancy is an unexplored field that has received increasing attention during the past years. The understanding of immune interactions during normal pregnancy could help guide the research of pregnancy-associated disorders such as PE what would finally allow the development of effective therapeutic tools.
Keywords
Korionske resice
Upala
Bolesti placente
Preeklampsija
T-limfociti
Stanice prirodne ubojice
Keywords (english)
Chorionic Villi
Inflammation
Placenta Diseases
Pre-Eclampsia
T-Lymphocytes
Natural Killer Cells
Language croatian
URN:NBN urn:nbn:hr:171:986525
Study programme Title: Basic and clinical medical sciences Study programme type: university Study level: postgraduate Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva, polje kliničke medicinske znanosti (doktor/doktorica znanosti, područje biomedicine i zdravstva, polje kliničke medicinske znanosti)
Type of resource Text
File origin Born digital
Access conditions Open access
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Created on 2023-05-12 07:33:42