The interaction between human leucocyte antigen-G and natural killer cells at the placental interface in HIV-1 infected pregnant women and the significance, if any, to in utero transmission.
| dc.contributor.advisor | Carpenter, S. | |
| dc.contributor.advisor | Bobat, Raziya Ahmed. | |
| dc.contributor.author | Moodley, Shamala. | |
| dc.date.accessioned | 2011-06-02T14:14:48Z | |
| dc.date.available | 2011-06-02T14:14:48Z | |
| dc.date.created | 2007 | |
| dc.date.issued | 2007 | |
| dc.description | Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2007. | en_US |
| dc.description.abstract | This study was undertaken to investigate the relationship between Natural Killer cells and HLA-G at the placental barrier in HIV-I infected pregnant women and to establish the significance, if any, to in utero infection. Fifty-five HIV -I infected pregnant women were recruited into the study after consent was obtained. Blood samples were collected from both mothers and babies for viral loads and CD4+ cell counts. Placental samples were obtained from pregnancies at delivery and examined by immunoperoxidase immunohistochemistry methods using monoclonal antibodies to p24 antigens and Natural Killer (CD56+) cells. HLA-G expression was quantified using real-time polymerase chain reaction. Analysis of viral loads and CD4+ cell counts were undertaken in categories. No significant association was observed between the viral load of mothers and their CD4+ cell counts. Eighteen percent of the women in this study population had 5 log viral loads with a transmission rate of 0.27(95% Cl, 0.15 - O. 39). Maternal viraemia was significantly associated with transmission of infection to babies (p = 0.047). The odds ratio indicated that for every 1 log increase in maternal viral load the babies were 3.1 times more likely to acquire the infection (Exp (B) = 3.137 (95%CI, 1.015-9.696). Furthermore, the study found that a higher number of female babies were infected than males. Although not statistically significant the odds ratio indicated that female babies were 3.1 times more likely to become infected than males (Exp (B) = 3.110 (95%CI, 0.819-11.808). We report here the results of immunohistochemistry for p24 antigens and NK (CD56+) cells and compare them to the immunological responses of both mothers and babies at birth. HIV-1 antigens were detected in 94.5% of all placentas by immunohistochemistry. Infiltration of CD56+ was found in 98% of placental tissue. The analysis revealed that the presence of p24 antigens in placental tissue was not influenced by maternal viral load or CD4+ cell counts. Lower median NK cell values were observed in placentas of mothers with infected babies as compared with the uninfected cluster. Although not statistically significant, the risk of vertical transmission was increased 3.4 times more in placentas which had lower NK cell values. According to the odds ratio, babies CD4+ counts were affected by every 1 log increase in mother's viral load. Overall, maternal viral load emerged as a strong predictor for risk of infection from infected mothers to their infants. Our analysis indicated that female babies were 3.7 times more likely to acquire the infection than males. Using data obtained from real-time PCR we investigated the relationship between maternal viral load and the quantity of HLA-G expression (p = 0.045; 95%CI 1.029- 11.499). Logistic regression models revealed that mother's viral load was the strongest risk factor for vertical transmission. No statistically significant correlation was noted with HLA-G and viral transmission. However, the odds ratio indicated that the risk of infection increased by 1.3 with every 1 fold increase in HLA-G expression. An analysis of mother-to-child transmission rates by gender revealed that the odds ratio for transmission was 3.4 times more in female babies than in males. We then investigated the relationship between maternal viraemia and HLA-G expression. A positive correlation between maternal viral load and placental HLA-G was observed (p = 0.038). When gender susceptibility to HLA-G expression was explored a statistically significant association was observed in placental tissue of mothers with infected and uninfected male babies and HLA-G expression (p = 0.013). To conclude, the analysis found that HLA-G was up regulated 3.95 times more in placental tissue of mothers with infected babies than in mothers with uninfected babies. | en_US |
| dc.identifier.uri | http://hdl.handle.net/10413/2989 | |
| dc.language.iso | en | en_US |
| dc.subject | AIDS (Disease)--Transmission. | en_US |
| dc.subject | Communicable diseases in pregnancy. | en_US |
| dc.subject | Foetus--Diseases. | en_US |
| dc.subject | HIV infections. | en_US |
| dc.subject | Perinatal haematology. | en_US |
| dc.subject | Newborn infants--Diseases. | en_US |
| dc.subject | Theses--Paediatrics and child health. | en_US |
| dc.title | The interaction between human leucocyte antigen-G and natural killer cells at the placental interface in HIV-1 infected pregnant women and the significance, if any, to in utero transmission. | en_US |
| dc.type | Thesis | en_US |