UBC Theses and Dissertations
Infection and immunity in pregnancy and preeclampsia Xie, Fang
Preeclampsia is a hypertensive disorder of pregnancy, which shares similar risk factors with atherosclerosis. There is increasing evidence to suggest that Chlamydia pneumoniae (C. pneumoniae) and cytomegalovirus (CMV) are linked with atherosclerosis and may trigger inflammation during pregnancy. However, the roles of these two microbes and the underlying immune mechanism remain unclear. Case control studies were preformed to examine the evidence of C. pneumoniae and CMV infection, immune response and Toll like receptor (TLR) gene variations in women with preeclampsia compared with normotensive intrauterine growth restriction (nIUGR), and normal pregnancy and non-pregnancy controls. At each stage, a systematic review and data synthesis methodology are applied to place our findings within the context of published studies in the area of C. pneumoniae and CMV infection and TLR gene variations in preeclampsia to clarify apparent discrepancies in these studies. In the first paper, an increase of C. pneumoniae genomic DNA loads was detected in preeclampsia when compared with normal pregnancy and non-pregnancy controls. Data synthesis indicated C. pneumoniae IgG seropositivity was more prevalent in preeclampsia patients. The second paper detected that preeclampsia had higher CMV IgG antibody level than normal pregnancies. Further, anti-CMV IgG seropositivity was more prevalent in women with preeclampsia than nIUGR and normal pregnancy controls. The third paper discussed up-regulated neutrophil TLR2 and TLR4 protein as well as mRNA expression in preeclampsia where the difference was more markedly in an early-onset preeclampsia condition. Early-onset preeclampsia was associated with elevated mRNA expression of cryopyrin, NF-kappaBp50, NF-kappaBp65 and IL-1β, as well as increased pro- versus anti-inflammatory cytokine ratios (TNF-α/IL-10 and IL-6/IL-10). Finally, in the fourth paper, data synthesis has suggested that gene variations in TLR2 or TLR4 were associated with early-onset preeclampsia. In summary, our findings indicated that infection with C. pneumoniae and CMV may trigger the maternal inflammation crossing the threshold development of preeclampsia. A better understanding of immunology and genetic basis of preeclampsia may reveal therapeutic opportunities for treatment of this disorder and lead to improved health for both mother and fetus.
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