Pro-Inflammatory Cytokine Levels in HIV Infected and Uninfected Pregnant Women with and without Preeclampsia.

INTRODUCTION: Preeclampsia and HIV/AIDS are inflammatory conditions that contribute significantly to adverse maternal and foetal outcomes. The immune reconstitution effects of HAART on inflammatory mediators has not been adequately studied in pregnancy and may impact on the inflammatory cytokine network in women with co-morbid preeclampsia. Our study evaluated changes in pro-inflammatory cytokines IL-2, TNF-α, IFN-γ and IL-6 in HIV infected preeclamptic women on HAART. METHODS: A prospective experimental study was conducted at Prince Mshiyeni Memorial Hospital between July 2013 and September 2014. One hundred and ninety three pregnant women were recruited into 4 groups: uninfected normotensive (50; 26%), infected normotensive (45; 23%), uninfected preeclamptic (53; 28%) and infected preeclamptic women (45; 23%). Serum levels of cytokines TNF-α, IFN- γ, IL-2 and IL-6 were determined using commercially available kits and a Cytometric Bead Array (CBA). Comparative data was recorded and analysed descriptively. RESULTS: In the control groups (normotensive), significantly lower values were found in IL-2 (p = 0.010), TNF-α (p = 0.045), and IL-6 (p = 0.005); and a non-significant decrease was observed in IFN-γ (p = 0.345) in HIV infected women on HAART compared to uninfected controls. In the experimental group (preeclamptic) women, significantly reduced levels were observed in IL-2 and TNF-α (p = 0.001; p = 0.000) and non-significant decreases were observed in IFN-γ and IL-6 (p = 0.023; p = 0.086) in HIV infected women on HAART compared with uninfected preeclamptic women. Non-significant differences were observed between uninfected preeclamptic and normotensive women. CONCLUSION: In uncomplicated/normotensive pregnancies, HIV/HAART is associated with significant decreases in IL-2, TNF-α and IL-6, and in preeclamptic women significant decreases in IL-2 and TNF-α were observed. These findings suggest that HIV/HAART impacts on pro-inflammatory cytokines in women with co-morbid preeclampsia. This provides a platform for further research on immune reconstitution effects of HAART during pregnancy, and the development of potential immune modulation therapies for the management of preeclampsia.

MicroRNA-146a rs2910164 is associated with severe preeclampsia in Black South African women on HAART.

BACKGROUND: South African (SA) Black women have a high prevalence of preeclampsia and HIV, both conditions associated with increased inflammation. miR-146a is an inflammatory-associated miR and a common single nucleotide polymorphism (rs2910164) has been associated with several disease conditions. To date, this SNP has not been investigated in SA Black women. We therefore aimed to investigate the miR-146a G > C SNP in SA Blacks with preeclampsia, and further examine possible association among preeclamptic (PE) women with HIV infection on HAART. METHODS: This hospital-based, case-control study included 95 normotensive and 98 PE Black SA women (aged 16-46 years old). Patients and controls were genotyped by PCR-RFLP. Using a Cytometric Bead Array assay, serum cytokine levels (including Th1- and Th2-related cytokines) were determined in 4 groups of pregnant women, viz: normotensive, HIV infected, PE + HIV infected, and PE women. RESULTS: There was no significant association between the miR-146a polymorphism and PE susceptibility in our data. However, in the subgroup analyses, the variant genotypes (GC/CC) were significantly associated with lower severe PE risk (p = 0.0497), more especially in the presence of HIV and HAART (p = 0.017). In the normotensive group, the variant genotypes were associated with lower IL-2 in both the total normotensive group (269 ± 1.26 (36) vs 273 ± 1.31 (23); p = 0.035) and the PE HIV+ sub-group 265 ± 1.54 (19) vs 271 ± 1.38 (11); p = 0.008). CONCLUSIONS: Our study suggests that miR-146a rs2910164 polymorphism might not be associated with PE susceptibility, cytokines or related features. However, the miR-146a GC/CC genotype might reduce susceptibility to severe PE, which might be further influenced by the presence of co-morbid HIV infection among pregnant women on HAART. This variant genotype may also be associated with reduced circulating IL-2 levels and thus reduced pro-inflammatory response in normotensive women, which may be further influenced by the presence of HIV infection and HAART.

microRNA-27a rs895819 is associated with obesity in HIV infected preeclamptic Black South African women on HAART.

BACKGROUND: Preeclampsia (PE) and HIV/AIDS present a major health challenge globally. South Africa has the highest disease burden of both HIV/AIDS and PE in the world. Despite extensive research, the pathophysiology of these conditions is not completely understood, however a genetic predisposition in women may affect susceptibility. MiRNA-27a regulates adipogenesis and glucose metabolism. A single nucleotide polymorphism (SNP) in miRNA-27a (rs895819T > C) has shown to have disparate effects in various populations. This study investigated the frequency of rs895819 in pregnant normotensive and preeclamptic Black South African (SA) women. METHODS: Enrollment into the study included: normotensive (n = 95; 45 HIV+; 80 analysed for rs895819T > C, age range: 16-46 years) and PE patients (n = 98; 45 HIV+; 56 analysed for rs895819T > C), age range: 16-42 years). DNA was isolated from peripheral blood mononuclear cells (PBMC). Genotyping of miRNA-27a rs895819 was detected using a TaqMan® SNP Genotyping assay. RESULTS: We did not find a significant association of miR-27a polymorphism with PE susceptibility in our data. However, in the subgroup analysis (based in HIV status), the variant genotypes (TC/CC) were associated with higher body mass index (BMI) among PE women (32.57 vs. 29.25, p = 0.064), significantly in the presence of HIV infection (33.47 vs. 27.8, p = 0.005). CONCLUSION: The results of this study suggests that miR-27a rs895819 may not be associated with PE susceptibility; however, the miR-27a TC/CC genotype increases susceptibility to elevated BMI in PE, which may be significantly influenced by co-morbid HIV infection among pregnant women on HAART.