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Title: Immune modulation in normal and pathological human pregnancy
Author: Granne, Ingrid Elizabeth
ISNI:       0000 0004 2743 9443
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2011
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The first half of this thesis addressed the clinical question of whether the phenotype of peripheral immune cells is affected by the normal menstrual cycle and whether there are differences in women with recurrent unexplained miscarriage. In chapter 2, a mid-luteal type 1 shift was demonstrated in NKdim and cytotoxic T cells in the menstrual cycle. In addition, women with recurrent miscarriage had increased numbers of type 1 (IL-18R+) cytotoxic lymphocytes and an increased number of NKdim and NKbright cells in the mid-luteal phase of the cycle. The shift to type 2 immunity seen in normal pregnancy has been previously identified from the second half of the first trimester. In chapter 3 this type 2 shift was seen in NK and T cells as early as 9 days post implantation. ST2L (the ligand for IL-33 and a marker of type 2 cells) was consistently up regulated at this very early stage post implantation in women who were pregnant. The second half of this thesis investigated IL-33 and ST2 in normal and pathological pregnancy. In chapter 4 it was shown that circulating IL-33 did not change over the course of pregnancy but that sST2 (the soluble decoy receptor) increased significantly in the 3rd trimester of normal pregnancy. Both IL-33 and ST2 were variably expressed by the pre-implantation human blastocyst, as well as by the 1st and 3rd trimester placenta. Finally, chapter 5 showed a potential role for ST2 in pre-eclampsia, an inflammatory disease of pregnancy. sST2 was significantly elevated in the third trimester in women who went on to develop pre-eclampsia even prior to the onset of disease. Using an in vitro model of placental perfusion, it was shown that sST2 can be secreted by the placenta, suggesting that sST2 may play a significant role in pregnancies complicated by this disease.
Supervisor: Sargent, Ian; Child, Tim Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Gynaecology ; Obstetrics ; pregnancy ; immunology ; NK cells ; recurrent miscarriage ; implantation