ItemPlacenta progesterone and its receptor in HIV-associated pre-eclampsia.(2022) Sewnarain, Serisha Azaria.; Naicker, Thajasvarie.; Singh, Shoohana.Background: The maintenance of a healthy pregnancy is dependent upon the placental production of progesterone, which interacts with progesterone receptors (PR) to stimulate trophoblast invasion. Pre-eclampsia (PE) is associated with defective trophoblast invasion, and due to the high prevalence of HIV infection and pre-eclampsia in South Africa, this study examined the expression of placental progesterone and PR in HIV-infected women with PE. Methods: Placental tissue from 180 women were grouped into normotensive (N) (n = 60) and PE (n =120). The PE group was further stratified by gestational age into early-onset pre-eclampsia (EOPE) and late-onset pre-eclampsia (LOPE) (n = 60 per group). Both normotensive and PE groups were stratified by HIV status (HIV positive+ and HIV negative-) into N- (n=30), N+ (n=30), EOPE- (n=30), EOPE+ (n=30), LOPE- (n=30) and LOPE+ (n=30). Immunohistochemistry and morphometric image analysis were used to assess placental progesterone and PR immuno-expression in exchange and conducting villi. The Mann Whitney test was used to compare the effects of pregnancy type (normotensive vs. pre-eclamptic), HIV status (HIV+ vs. HIV-) and PE subtype (EOPE vs LOPE). For comparative analysis across all six study groups, a one-way ANOVA non-parametric Kruskal-Wallis test was used, followed by Dunn's Multiple Comparisons test. A two-way ANOVA was used to compare villi type (exchange vs conducting) and pregnancy type. Results: Progesterone was immunoexpressed within endothelial, mesenchymal and trophoblast cells within conducting and exchange villi whilst PR was mainly expressed on cytotrophoblasts and syncytiotrophoblasts. Progesterone and PR immuno-expression in exchange villi were significantly lower in the following groups: PE compared to the normotensive group (p = <0.0001 and p = <0.0001, respectively) and EOPE compared to the LOPE group (p = <0.0001 and p = <0.0001). Progesterone immuno-expression in the HIV+ group compared to the HIV- group was significantly lower (p = <0.0001), whilst PR expression was non-significant (p = 0.4291). Progesterone and PR immuno-expression in conducting villi were downregulated in the following groups: EOPE group compared to the LOPE group (p = <0.0001 and p = <0.0001) and in the HIV+ group compared to the HIV- group (p = <0.0001 and p = 0.0009). Progesterone immunoexpression was higher in the PE group compared to normotensive (p = 0.0326) and PR immunoexpression was non-significant (p = 0.6935). xiii There was a significant difference in progesterone and PR in exchange vs conducting villi (p = <0.0001 and p = <0.0001, respectively) and villi type accounted for 34.47% and 15.28% of total variance for progesterone and PR, respectively. Conclusion: This study observed a reduction in progesterone and PR immunoexpression in the exchange villi of pre-eclamptic placenta. Progesterone and PR immuno-expression were also significantly reduced in HIV+ placentas, with the EOPE+ group displaying the lowest immunoexpression. We postulate that HIV infection combined with cART may cause mitochondrial dysfunction that compromises progesterone synthesis. Progesterone deficiency results in minimal binding to PRs, which affects signalling pathways (PI3K/AKT, JAK-STAT, and MAPK cascades) and impairs trophoblast invasion. Notably, the EOPE group has the lowest immunoexpression of progesterone and PRs which links the downregulation of progesterone to defective placentation. This study links HIV infection to reduced progesterone production during pregnancy and associates decreased progesterone and PR immuno-expression with PE. Isendlalelo: Ukugcinwa kokukhulelwa okunempilo kuncike ekukhiqizweni kwe-placenta yeprogesterone, esebenzisana nama-progesterone receptors (PR) ukuze kuvuse ukuhlasela kwetrophoblast. I-Pre-eclampsia (PE) ihlotshaniswa nokuhlasela kwe-trophoblast enesici, futhi ngenxa yokusabalala okuphezulu kokutheleleka nge-HIV kanye ne-pre-eclampsia eNingizimu Afrika, lolu cwaningo luhlole ukuvezwa kwe-placental progesterone kanye ne-PR kwabesifazane abane-HIV abane-PE. Izindlela: Izicubu ze-placental ezivela kwabesifazane abangu-180 zahlanganiswa zaba yinormotensive (n = 60) ne-PE (n = 120). Iqembu le-PE laphinde lahlukaniswa ngeminyaka yokukhulelwa yaba yi-PE yokuqala kanye ne-PE yokufika sekwephuzile (n = 60 iqembu ngalinye). Womabili amaqembu e-normotensive kanye ne-PE ahlukaniswa ngesimo se-HIV (HIV+ ne-HIV negative-) aba yi-N- (n=30), N+ (n=30), EOPE- (n=30), EOPE+ (n=30), LOPE - (n=30) kanye ne-LOPE+ (n=30). I-Immunohistochemistry kanye nokuhlaziywa kwesithombe semorphometric kwasetshenziselwa ukuhlola i-placenta progesterone kanye ne-PR immunoexpression ekushintsheni nasekuqhubeni i-villi. Imiphumela: I-progesterone yayingabonakali ngaphakathi kwamaseli e-endothelial, mesenchymal kanye ne-trophoblast ngaphakathi kokuqhuba nokushintshanisa i-villi ngenkathi i- PR iboniswa ikakhulukazi kuma-cytotrophoblasts nama-syncytiotrophoblasts. I-progesterone ne- PR immuno-expression ekushintsheni i-villi yayiphansi kakhulu kumaqembu alandelayo: I-PE uma iqhathaniswa neqembu le-normotensive (p = <0.0001 kanye ne-p = <0.0001, ngokulandelana) kanye ne-EOPE uma kuqhathaniswa neqembu le-LOPE (p = <0.0001 kanye p = <0.0001). I-progesterone immuno-expression eqenjini le-HIV+ uma iqhathaniswa neqembu le- HIV yayiphansi kakhulu (p = <0.0001), kuyilapho inkulumo ye-PR yayingabalulekile (p = 0.4291). I-progesterone ne-PR immuno-expression ekuqhubeni i-villi yehlisiwe emaqenjini alandelayo: Iqembu le-EOPE uma liqhathaniswa neqembu le-LOPE (p = <0.0001 kanye ne-p = <0.0001) naseqenjini le-HIV+ uma liqhathaniswa neqembu le-HIV (p = <0.0001 futhi p = 0.0009). Iprogesterone immuno-expression yayiphezulu eqenjini le-PE uma kuqhathaniswa nenormotensive (p = 0.0326) kanye ne-PR immuno-expression yayingabalulekile (p = 0.6935). xv Kunomehluko omkhulu ku-progesterone ne-PR ekuhwebeni ngokuqhudelana nokuqhuba i-villi (p = <0.0001 kanye ne-p = <0.0001, ngokulandelana) kanye nohlobo lwe-villi lubalelwa ku- 34.47% no-15.28% wokuhluka okuphelele kwe-progesterone ne-PR, ngokulandelana. Isiphetho: Lolu cwaningo lubone ukuncipha kwe-progesterone kanye ne-PR immunoexpression ku-villi yokushintshanisa ye-pre-eclamptic placenta. I-progesterone ne-PR immuno-expression nazo zehliswa kakhulu kuma-placenta e-HIV+, neqembu le-EOPE+ libonisa ukubonakaliswa okuphansi kokuzivikela komzimba. Sibeka umbono wokuthi ukutheleleka nge-HIV kuhlanganiswe ne-cART kungase kubangele ukungasebenzi kahle kwe-mitochondrial okuphazamisa ukwakheka kwe-progesterone. Ukuntuleka kwe-progesterone kubangela ukubophezela okuncane kuma-PRs, okuthinta izindlela zokubonisa (PI3K/AKT, JAK-STAT, kanye ne-MAPK cascades) futhi kulimaze ukuhlasela kwe-trophoblast. Ngokuphawulekayo, iqembu le-EOPE line-immuno-expression ephansi kakhulu ye-progesterone kanye ne-PRs exhumanisa ukulawulwa kwe-progesterone nokuzala okungalungile. Lolu cwaningo luxhumanisa ukutheleleka nge-HIV nokuncipha kokukhiqizwa kwe-progesterone ngesikhathi sokukhulelwa kanye nokuhlotshaniswa nokuncipha kwe-progesterone kanye ne-PR immuno-expression ne-PE. ItemCell signalling of the epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) axis in HIV associated pre-eclampsia.(2021) Laldeo, Arisha.; Naicker, Thajasvarie.; Singh, Shoohana.Background: Epidermal growth factor is a protein which, when bound to epidermal growth factor receptor, facilitates cell proliferation and differentiation, hence is vital for a successful normal pregnancy. In preeclampsia (PE), EGFR signalling is dysregulated leading to decline in blood flow to the fetus. Furthermore, aberrant EGF/EGFR signalling leads to deficient trophoblast development. The Trans-Activator of transcription (Tat) protein, displayed in HIV inhibits EGF related processes. Since PE and HIV infection are the leading causes of both maternal morbidity and mortality in South Africa; this study focuses on examining EGF/EGFR signalling in HIV associated PE and their effect on downstream targets. Methods: Post ethics approval; this study selected 80 pregnant women from an archive of retrospectively stored serum samples. The samples were stratified by type of pregnancy and HIV status into the following groups: a) HIV negative preeclamptic women (n=20), b) HIV positive preeclamptic women (n=20), c) HIV negative normotensive pregnant women (n=20) and d) HIV positive normotensive pregnant women (n=20). Both EGF and EGFR were multiplexed in a Bioplex immunoassay technique to determine their serum concentration across study groups at term. Results: Based on the clinical data, statistically significant differences were obtained across groups for gestational age (p < 0.001), birth weight (p < 0.001), systolic BP (p < 0.001), BMI (p = 0.048), diastolic BP (p < 0.001) and maternal weight (p = 0.002). However, no statistical significance was observed for maternal age across all study groups (p = 0.065). A significant decline in EGF levels were observed in PE compared to normotensive pregnancy, regardless of HIV status (p = 0.0214). Based on HIV status, no statistical significance in EGF concentration was observed (p = 0.6593). EGFR was significantly elevated in normotensive pregnant compared to preeclamptic women (p < 0.0001) (Figure 2A). In contrast, there were no significant differences of EGFR based on HIV status alone (p = 0.2092) (Figure 2B). However, a significant up-regulation of EGFR was observed between normotensive HIV positive compared to PE HIV positive women. Normotensive HIV negative was also significantly up-regulated compared to PE HIV positive (p < 0.0001). Normotensive HIV positive was significantly higher than PE HIV negative. Also, of note within the PE group, HIV negative EGFR levels were significantly up-regulated compared to the HIV positive group. Conclusion: This novel study outlines a significant down-regulation of EGF and EGFR in PE compared to normotensive pregnant women; regardless of HIV status. No significant differences were observed based on HIV status alone for serum EGF levels. This could be due to immune reconstruction as all HIV infected patients received HAART, hence may have neutralised EGF levels. Furthermore, these findings may be attributed to the Trans-Activator of transcription (Tat) protein which prevents EGF related function. However, for serum EGFR concentration there were significant differences within PE group based on HIV status. Significant differences were observed between normotensive and preeclamptic based on HIV status, except for normotensive HIV negative vs PE HIV negative. Furthermore, there was no significance in the normotensive group based on HIV status. The decreased levels of serum EGF/ EGFR could possibly be used as a biomarker for PE development during pregnancy. Isendlalelo: I-Epidermal growth factor iyiphrotheni okuthi uma ihlangene ne-epidermal growth factor receptor, isiza ngokwandisa amaseli nokuwehlukanisa, yingakho ibalulekile ekukhulelweni okujwayelekile okuphumelelayo. Ku-preeclampsia (PE), ukusayinda kwe-EGFR kuyaphazamiseka okuholela ekwehleni kokugeleza kwegazi ku-fetus. Ngaphezu kwalokho, ukusayina kwe-EGF / EGFR ngendlela eyehlukile kunalena eyejwayelekile kuholela ekushodeni kwe-trophoblast. I-Trans-Activator of transcription (Tat) protein ivimbela izinqubo ezihlobene ne-EGF uma ihlangene neHIV. Njengoba izifo ze-PE kanye ne-HIV kuyizimbangela ezihamba phambili zokugula nokufa komama eNingizimu Afrika; lolu cwaningo lugxile ekuhloleni ukusayina kwe-EGF / EGF-R ku-PE ehlobene ne-HIV kanye nomphumela wazo uma zixhuma endaweni eziyihlosile maphansi neseli. Izindlela: Ngemva kokugunyazwa kokuziphatha; lolu cwaningo lukhethe abesifazane abakhulelwe abangama-80 kungobo yomlando yamasampula e-serum agcinwe ngokudlule. Amasampula ahlukaniswa ngohlobo lokukhulelwa kanye nesimo se-HIV emaqenjini alandelayo: a) abesifazane abakhulelwe abangenayo i-HIV kodwa abanomfutho wegazi ophakeme (n=20), b) abesifazane abakhulelwe abane-HIV nomfutho wegazi ophakeme (n=20), c) abesifazane abakhulelwe abangenayo i-HIV futhi abanomfutho wegazi ojwayelekile (n=20), kanye d) nabesifazane abakhulelwe abane-HIV kodwa banomfutho wegazi ojwayelekile (n=20). Kokubili i-EGF ne-EGF-R zacwaningwa ngendlela ye-Bioplex immunoassay ukuze kutholwe inani lweserum yazo kuwo wonke amaqembu ocwaningo ngesikhathi. Imiphumela: Ngokubuka idatha esungulwe yimtholampilo, umehluko obalulekile ngokwezibalo watholwa kuwo wonke amaqembu eminyaka yobudala (p <0.001), isisindo sokuzalwa (p <0.001), i-systolic BP (p <0.001), BMI (p = 0.048), i-diastolic BP (p <0.001) kanye nesisindo sikamama (p = 0.002). Kodwa-ke awukho umehluko omkhulu ngokwezibalo owabonwa ngeminyaka yobudala bomama kuwo wonke amaqembu ocwaningo (p = 0.065). Ukwehla ngokwezibalo okubalulekile kwe-EGF kwabonwa i-PE uma kuqhathaniswa nokukhulelwa kwe-normotensive, kungakhathaliseki isimo se-HIV (p = 0.0214). Ngokubuka isimo se-HIV, akukho ukubaluleka kwezibalo kwe-EGF okuphawulwe (p = 0.6593). Kungakhathalekile ukuthi ngabe i-HIV ithini, i-EGFR iphakanyiswe kakhulu kumanormotensive abakhulelwe ngokuqhathaniswa nabesifazanebe-preeclamptic (p < 0.0001). Ngokuphambene, kwakungekho umehluko ophawulekayo we-EGFR ngokusekelwe esimweni se-HIV (p = 0.2092). Kodwa-ke, ukulawulwa okubalulekile kwe-EGFR kwabonwa phakathi kwe-HIV positive normotensive uma kuqhathaniswa nabesifazane abakhulelwe abangenayo ixvi HIV (p = 0.001); ngaleyo nkathi ukwehla okubalulekile kwe-EGFR kwaboniswe kuwo wonke amaqembu ocwaningo (p = 0.001). Isiphetho: Lolu cwaningo lwenoveli luveza ukwehla okubalulekile kwe-EGF ne-EGFR ku-PE uma kuqhathaniswa nabesifazane abakhulelwe abajwayelekile; kungakhathaliseki isimo se-HIV. Awukho mehluko omkhulu obonwe ngokusekelwe esimweni se-HIV. Lokhu kungase kube ngenxa yokwakhiwa kabusha kwamasosha omzimba njengoba zonke iziguli ezine-HIV zithole i-HAART, yingakho kungase kulinganise amazinga e-EGF/EGFR. Ngaphezu kwalokho, lokhu okutholakele kungase kubalulwe ku-Trans-Activator of transcription (Tat) protein evimbela umsebenzi ohlobene ne-EGF. I-down-regulation ye-EGF/EGFR ingase isetshenziswe njengokuhlola inkomba yokubikezela ukuthuthukiswa kwe-PE ngesikhathi sokukhulelwa. ItemThe regulation of Osteopontin and soluble Neuropilin-1 in HIV- associated preeclampsia.(2020) Naidoo, Nitalia.; Naicker, Thajasvarie.Background: The prevalence of preeclampsia (PE) and human immunodeficiency virus (HIV) infection in pregnant women remains a concern to the South African healthcare system. The conflicting angiogenic roles of osteopontin (OPN) and soluble neuropilin-1 (sNRP-1) has been highlighted in many diseases. However, there is a dire paucity of data on the influence of OPN and sNRP-1 in PE. Moreover, there is an absence of information of OPN and sNRP-1 in HIV-associated PE. In light of the aforementioned criteria, it was important to study the influence of OPN and sNRP-1 in the synergy of HIV-infection and PE. Therefore, this study evaluated the concentration of angiogenic proteins, OPN and sNRP-1, in the synergy of HIV infection and PE. Additionally, in light of the coronavirus disease 2019 (COVID-19) pandemic, we reviewed maternal endothelial dysfunction in HIV-associated PE comorbid with COVID-19. In this review article, we also explored the potential of antiretroviral therapy (ART) in the therapeutic intervention of COVID-19. Study design: A Bio-plex multiplex immunoassay was used to quantify serum OPN and sNRP-1 concentrations in preeclamptic vs normotensive pregnancy type stratified by HIV status (n=19 per subgroup). Results: Significant differences across all groups, i.e., HIV-negative normotensive (n = 19), HIV-negative preeclamptic (n = 19), HIV-positive normotensive (n = 19) and HIV-positive preeclamptic (n = 19), were reported in maternal age (p = 0.0211), gestational age (p = 0.0004), parity (p = 0.0042), systolic blood pressure (p < 0.0001) and diastolic blood pressure (p < 0.0001). The concentration of OPN was significantly downregulated by pregnancy type (preeclamptic vs normotensive; p = 0.0033) and showed a non-significant elevation when stratified by HIV status (HIV-positive vs HIV-negative; p = 0.5099). In addition, there was a significant upregulation in sNRP-1 concentration by pregnancy type (preeclamptic vs normotensive; p = 0.0054) and by HIV status (HIV-positive vs HIV-negative; (p = 0.0005). In comparison to the normotensive HIV-negative group, there was a significant difference in sNRP-1 concentrations between the sub-groups normotensive HIV-positive (p = 0.0049), preeclamptic HIV-negative (p = 0.0244), and preeclamptic HIV-positive (p < 0.001), respectively. Conclusion: This innovative study validates a significant systemic downregulation of OPN in PE compared to normotensive pregnancies in contrast to an upregulation of sNRP-1, conforming to the anti-angiogenic milieu of PE. Moreover, based on HIV-status, both the systemic OPN and sNRP-1 levels were upregulated in HIV-positive pregnancies. This may be attributed to the HIV trans-activator of transcription protein mimicry of VEGF and/or the immune reconstitution following ART as well as to integrin expression that mediates endothelial cell tube formation during angiogenesis. Additionally, adverse effects associated with HIV infection and ART promote endothelial dysfunction predisposing PE development; however, higher prevalence and mortality rates among PE cases are still associated with ART use. Pregnancies complicated by the COVID-19 exploitation of angiotensin-converting enzyme 2 have a strong correlation with PE-like symptoms such as endothelial injury, implicating COVID-19 in PE onset. Inconsistent data on the potential effectiveness of ART in COVID-19 and their safety in pregnancy warrants further investigations. ItemThe role of complement components C2 and C5a in HIV associated preeclampsia.(2020) Govender, Sumeshree.; Naicker, Thajasvarie.Background: In South Africa (SA), HIV infection and preeclampsia (PE) are the leading causes of maternal mortality and morbidity. In PE, immunologic maladaptation alters fetal tolerance. Our first line of defence against pathogens is controlled by the complement system, a central part of our innate immunity. In the complement cascade, complement component 5a (C5a) is a potent proinflammatory anaphylatoxin, whilst complement component 2 (C2) defends the onset of infections and immune complex removal. There is a dearth of information on these proteins in the synergy of HIV infection and PE development. In light of the high prevalence of HIV infection and PE in SA, the aim of this study was to determine the concentrations of C2 and C5a in HIV associated normotensive versus preeclamptic pregnancies. Method: Post ethics approval, stored serum samples were obtained from 76 pregnant women and grouped according to pregnancy type, preeclamptic patients (n=38) and normotensive patients (n=38), this was further stratified by HIV status, normotensive HIV-positive (n=19), normotensive HIV-negative (n=19), preeclamptic HIV-positive (n=19), and preeclamptic HIV-negative (n=19). All HIV-infected patients received (Highly Active Antiretroviral Therapy) HAART. The expression of C5a and C2 was quantified using Bio-Plex multiplex immunoassay. Results: Based on pregnancy type, a significant downregulation of C5a concentration was demonstrated in the preeclamptic vs normotensive pregnancies regardless of HIV status (p = 0.0486). There was no statistical significance in C5a concentration between the HIV-positive and HIVnegative groups, irrespective of pregnancy type (p = 0.8002). Furthermore, there was no significant difference in C2 levels between preeclamptic vs normotensive group, regardless of HIV status. Similarly, based on HIV status, no statistical significance regardless of pregnancy type was found (p = 0.7469). Conclusion: This novel study demonstrates a significant decrease in the concentration of C5a in PE compared to normotensive pregnant women. This unexpected expression may be due to the rapid consumption of C5a in circulation, an altered affinity of C5a to its receptors or genetic polymorphisms. We also report similar C5a and C2 concentrations between HIV positive and HIV negative groups possibly reflecting the immune reconstitution effect of HAART. Complement dysregulation affects host innate defence in PE by exaggerating placental and fetal injury hence requires a large-scale study to evaluate individual proteins of the complement cascade in the synergy of HIV associated preeclampsia. ItemThe function of Adipsin and C9 protein in the complement system in HIV-associated preeclampsia.(2020) David, Mikyle.; Naicker, Thajasvarie.; Moodley, Jagidesa.Background Hypertensive disorders of pregnancy (HDP) and non-pregnancy related diseases (HIV, TB) are the most common causes of maternal mortality in South Africa (SA). Preeclampsia (PE), a complex medical disorder, accounts for the majority of maternal deaths emanating from HDP. In SA, the prevalence of HIV infection in pregnancy is high. The complement system, a part of our innate response, may be altered in the synergy of HIV infection and PE development. Complement activation at the maternal-interface may exacerbate inflammation, tissue injury, apoptosis as well as vascular leakage, in the complicated state of PE. The complement proteins, adipsin and C9, activates the body’s natural defence against HIV infection. C9 functions as a pore-forming component of the membrane attack complex. Moreover, the high rollout in SA of antiretroviral therapy may affect the immune response in HIV infected women. This study investigates the concentration of the complement proteins, Adipsin and C9 in the duality of HIV-associated PE. Method Samples of 38 normotensive and 38 preeclamptic patients, stratified further by HIV status were collected from a regional hospital. Thereafter, analysis of analytes via the Bio-plex Multiplex immunoassay occurred. Results Maternal weight did not differ (p = 0.1196) across the study groups. The concentration of adipsin was statistically different between the PE vs normotensive pregnant groups, irrespective of HIV status (p = 0.0439). There was no significant difference in adipsin concentration between HIV-negative vs HIV-positive groups, irrespective of pregnancy type (p = 0.6290). Additionally, there was a significant difference in adipsin concentration between HIV negative normotensive vs HIV negative preeclampsia (p < 0.05), as well as a difference between HIV negative preeclampsia vs HIV positive preeclampsia (p < 0.05). C9 protein expression was not statistically different between the normotensive and PE groups, regardless of HIV status (p =0.5365). No statistical significance in C9 expression was found between HIV positive vs HIV negative groups, regardless of pregnancy type (p = 0.3166). Similarly, no statistical significance was noted across all study groups (p= 0.0774). Conclusion This study demonstrates a significant up-regulation of adipsin in PE compared to normotensive pregnancies; this finding correlates with the exaggerated inflammatory milieu of PE. Complement C9 protein was similar between pregnancy types. This similarity may emanate from properdin dysregulation or a genetic polymorphism. The concentration of adipsin and C9 proteins were not affected by HIV status due to the immune reconstitution effect of antiretroviral therapy. Furthermore, the up-regulation of adipsin in placental sites and urinary levels of PE in previous studies, in tandem with our findings, indicate the possibility of adipsin as a predictor value for PE development. ItemThe regulation of sVEGFR-2 and sVEGFR-3 in the serum of pregnant women with HIV- related Pre-eclampsia recieving antiretroviral therapy.(2020) Abel, Tashlen.; Naicker, Thajasvarie.Background: An imbalance in the concentration of pro- and anti-angiogenic factors is evident in preeclampsia (PE). This study evaluated the expression of soluble vascular endothelial growth factor receptor 2 (sVEGFR-2) and sVEGFR-3 in the serum of preeclamptic compared to normotensive women complicated by Human Immunodeficiency Virus (HIV) infection. Additionally, in light of the coronavirus disease 2019 (COVID-19) pandemic, maternal and foetal health is a great concern; hence, we have composed a review article that provides an insight into the synergy of PE, HIV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, as well as the involvement of epigenetic regulation. Method: The serum expression of sVEGFR-2 and sVEGFR-3 in preeclamptic vs normotensive pregnancies, stratified by HIV status (n = 19) was evaluated through the utilization of a Milliplex Multiplex immunoassay. Results: In comparison to normotensive (HIV-negative and HIV-positive), gestational age (p = 0.0004), systolic and diastolic blood pressure (p<0.0001) , and parity (p = 0.0042) were significantly different in preeclamptic (HIV-negative and HIV-positive) pregnancies. The serum expression of sVEGR-2 was significantly downregulated in PE compared to normotensive pregnancies (p = 0.0025), regardless of HIV status. A downward trend in the concentration of sVEGFR-3 was observed in preeclamptic women (p = 0.0586), irrespective of HIV status. Across all groups, the concentration of sVEGFR-2 was significantly downregulated in HIV-positive PE (p = 0.0053) and the expression of sVEGFR-3 was significantly reduced in HIV-negative PE (p = 0.0393), compared to HIV-negative PE. Conclusion: This novel investigation reports a significant downregulation of serum sVEGFR-2 and a downward trend in the serum expression of sVEGFR-3 in preeclamptic compared to normotensive pregnancies. The hypoxic microenvironment of PE is associated with endothelial cell damage which greatly contributes to the decreased serum expression of sVEGFR-2 and sVEGFR-3. The use of antiretroviral therapy (ART) reconstitutes the immune response in HIV-positive preeclamptic women; hence, it significantly contributes to the risk of developing PE. Furthermore, the HIV-1 trans-activator of transcription protein mimics the behaviour of vascular endothelial growth factors (VEGF) due to their structural homology; however, this does not counterbalance the decline of VEGF in PE due to the administration of ART. In addition, the association of pregnancy with an upregulation of angiotensin converting enzyme 2 receptors increases the risk of pregnant women being infected with SARS-CoV- 2. Further investigations are essential to critically evaluate the influence of HIV infection and the epigenetic regulation of these soluble anti-angiogenic factors. ItemThe role of basic fibroblast growth factor in HIV associated preeclampsia.(2018) Sangany, Charline Mukasa.; Naicker, Thajasvarie.Background: In South Africa, hepatitis B virus (HBV) infection remains a major cause of morbidity and mortality, however, little is known about the prevalence and distribution of HBV in some regions and populations. Methods: This secondary analysis is based on 9791 participants (15-49 years old) enrolled in the HIV incidence Provincial Surveillance System (HIPSS); a population-based household study undertaken from June 2014 to June 2015 in the Vulindlela (rural) and Greater Edendale (periurban) areas of the uMgungundlovu district, KwaZulu-Natal (KZN), South Africa. Interviewer administered questionnaires were completed to obtain demographic, psychosocial, behavioural and clinical information. Peripheral blood samples were collected and sera were tested for hepatitis B surface antigen (HBsAg) and all samples testing positive were further tested for hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe). The estimated weighted seroprevalence of HBV markers was calculated and the association of HBsAg with sociodemographic and behavioural factors measured. Results: The overall HBsAg prevalence was 4.0% (95% confidence interval (CI) 3.4-4.5); 4.8% (95% CI 3.8- 5.8) in men and 3.2% (95% CI 2.5-3.9) in women, P=0.01. Among HBsAg positive participants, 35.2% (95% CI 29.2-41.2) were HBeAg positive and 66.3% (95% CI 60.1-72.4) were anti-HBe positive. Among men 15-19 years old HBeAg seroprevalence was 92.2% (95% CI 75.8-100) compared to 4.4% (95% CI 0-13.7) in women in the same age group; P <0.01. HBsAg prevalence was 6.4% (95% CI 5.3-7.5) among HIV positive participants compared to 2.6% (95% CI 1.9-3.2) among HIV negative participants, (P<0.01) and was higher among HIV positive men 8.7% (95% CI 6.3-11.2) compared to HIV positive women 5.0% (95% CI 3.8-6.2), P<0.01. Conclusion: HBV infection, particularly among HIV positive men remains an important public health problem in rural and periurban communities in KwaZulu-Natal, South Africa. The prevalence of HBsAg and HBeAg highlight the importance of surveillance and an important missed opportunity for the scale up of programmes to achieve the goal of controlling HBV for public health benefit. ItemThe role of soluble e-selectin and thrombospondin-2 in HIV associated preeclampsia.(2019) Naidoo, Girija.; Naicker, Thajasvarie.Objective: HIV infection and hypertensive disorders of pregnancy are common causes of maternal mortality in South Africa. Preeclampsia (PE) is a pregnancy-specific disorder that contributes to the majority of maternal deaths caused by hypertension in pregnancy. Reduced placentation, endothelial dysfunction of multiple organs and inflammation occur during PE. Endothelial cells express the adhesion molecule soluble E-selectin (sE-selectin) in response to inflammation. This molecule facilitates the cohesion of leukocytes to endothelial cells. In PE, endothelial cell activation and dysfunction cause endothelial cells to secrete the glycoprotein thrombospondin-2 (TSP-2). TSP-2 affects cellular functions, plays a regulatory role in the extracellular matrix and is an inhibitor of angiogenesis. In PE, an imbalance of angiogenic and anti-angiogenic factors result in dysregulation of angiogenesis. Considering the high rate of maternal mortality in South Africa due to HIV infection and PE, the aim of this study was to investigate the role of sE-selectin and TSP-2 in HIV-associated preeclamptic and normotensive pregnancies. Method: The study population (n = 72) comprised of normotensive pregnant (n = 36) and preeclamptic (n = 36) groups. These groups were further stratified by HIV status (negative vs. positive). The Bio-Plex immunoassay technique was used to measure serum concentrations of sE-selectin and TSP-2. Results: There was a statistical difference observed in gestational age, systolic blood pressure, diastolic blood pressure and baby weight across the study groups (p < 0.0001). sE-selectin: Based on pregnancy type and HIV status, levels of serum sE-selectin were significantly increased in preeclamptic HIV-negative compared to normotensive HIV-negative groups (p = 0.0070). TSP-2: Regardless of HIV status and based on pregnancy type, TSP-2 levels were significantly elevated (p = 0.0429) in preeclamptic compared to normotensive groups. Based on HIV status, a significant upregulation (p = 0.0095) of TSP-2 was noted in HIV-positive compared to HIV-negative groups. Furthermore, based on pregnancy type and HIV status, levels of TSP-2 were statistically significant across all study groups (p = 0.0229). Conclusion: This study highlights the role of sE-selectin and TSP-2 in preeclamptic women compromised by HIV infection and demonstrates the potential biomarker value of sE-selectin and TSP-2 in the early diagnosis of preeclampsia. ItemThe role of Vascular Endothelial growth factor receptor-3 in the placenta in HIV associated preeclampsia.(2019) Pillay, Saieshni.; Naicker, Thajasvarie.Summary: PE and HIV dualism in pregnant HAART women are yet to be investigated. Furthermore, the effect on VEGFR-3 and subsequent downstream influence on angiogenesis is poorly understood. Therefore, this investigation evaluates the immuno-expression of VEGFR-3 in placental conducting and exchange villi from normotensive, preeclamptic and HIV+ African women, using morphometric image analysis. Study design: This is a prospective study utilizing retrospectively collected, paraffin wax-embedded, placental samples (n=90) that were immuno-stained for VEGFR-3. The study population consisted of normotensive (n=30) and pre-eclamptic (n=60) groups which were further stratified on the basis of HIV status (negative - and positive +), and early and late onset preeclampsia (EOPE and LOPE respectively). The final groups were as follows; N- (n=15), N+ (n=15), EOPE- (n=15), EOPE+ (n=15), LOPE- (n=15) and LOPE+ (n=15). Brightfield microscopy and morphometric image analysis of VEGFR-3 immuno-expression within conducting and exchange placental villi was performed. Results: HIV status analysis did not demonstrate a significant difference in VEGFR-3 immunostaining for both villous types. The N vs. PE comparative analysis showed a downregulated immuno-expression of VEGFR-3 in both conducting (p = 0.0107) and exchange (p < 0.0001) villi. Results from analysis of pregnancy subtypes showed a significant difference in VEGFR-3 expression between N vs. EOPE regardless of villous type. Conclusion: This study demonstrates that HIV infection does not significantly alter VEGFR-3 placental immuno-expression in pregnant women receiving HAART irrespective of pregnancy type. Furthermore, VEGFR-3 immuno-expression was dysregulated in EOPE women, irrespective of HIV status. These novel findings emphasize severe down-regulation of VEGFR-3 in preeclamptic women, and provide compelling evidence for a future investigation into placental angiogenic and lymphangiogenic regulation in the early onset of PE. Isifinyezo: Inhlanganyela yePE neHIV kwabesifazane abakhulelwe abemukela iHAART kusamele kuphenywe. Ngakho-ke, lolu phenyo luhlola ukubonakaliswa kwe-VEGFR-3 kwiplacental ekuqhubeni nasekushintshaniseni i-villi kusuka ku-normotensive, preeclamptic ne-HIV+ kwabesifazane abansundu, kusetshenziswa ukuhlaziywa kwezithombe. Umklamo wokutadisha: Lokhu kucwaninga okungenzeka kusetshenziswa amasampula eplacental aqoqiwe, afakwe kwi-paraffin wax (n=90) abegcinelwe i-immuno-stain for VEGFR-3. Inani labantu abacwaningwayo liqukethe amaqembu: i-Normotensive (n=30) kanye ne-pre-eclamptic (n = 60) abephinde ahlukaniswa ngesisekelo sesimo se-HIV (abangenayo i-HIV Kanye nabanayo i-HIV+), kanye nabaqalwa yi-preeclampsia nalabo abakhombisa i-preeclamsia emva kwesikhathi eside (i-EOPE ne-LOPE) ngokulandelana. ). Amaqembu esewonke ngokulandelayo; N- (n=15), N+ (n=15), EOPE- (n=15), EOPE+ (n=15), LOPE- (n=15) no-LOPE+ (n=15). IBrightfield microscopy nokuhlaziywa kwezithombe imorphometric yeVEGFR-3 nokuziveza kwayo ngokuqhuba nokushintshaniswa kweplacental villie kwenziwa. Imiphumela: Ukuhlaziywa kwesimo seHIV akuvezanga umehluko omkhulu kwiVEGFR-3 immuno-staining kuzo zombili izinhlobo zeVillous. Ukuhlaziywa kokuqhathaniswa kwe-N vs. PE kukhombise ukubonakaliswa okuphansi kwe-immuno-expression kwe-VEGFR-3 kokubili kuqhuba (p = 0.0107) kanye nokushintshaniswa (p < 0.0001) villi. Imiphumela yokuhlaziywa kwezinhlobo ezahlukene zokukhulelwa zikhombise omkhulu umehluko ekubonisweni kweVEGFR-3 phakathi kwe N iqhathaniswa neEOPE kungakhathaleleki uhlobo lwevillous. Isiphetho: Lomkamo ukhombisa ukuthi ukutheleleka nge HIV akunawo umthelela omkhulu ekuvimbeni iVEGFR-3 immuno-expression kwabesifazane abakhulelwe abemukela iHAART kungakhathalaleki uhlobo lokukhulelwa. Ngaphezu kwalokho, iVEGFR-3 immuno-expression kwabesifazane abaneEOPE ayisebenzanga, kungakhathaleki isimo sabo seHIV. Okutholakale emibhalweni lugcozelela ngokukhulu ukwehla kwezinga kweVEGFR-3 kwabesifazane aba-preeclamptic, futhi kunikeza ubufakazi obuqanda ikhanda obungasetshenziswa kucwaningo oluzayo kweplacental angiogenic nelymphangiogenic regulation kulabo abaqedwa yiPE. ItemThe role of Endothelin-1 in HIV associated pre-eclampsia.(2019) Mthembu, Mbuso Herald.; Naicker, Thajasvarie.Introduction and Background: Preeclampsia (PE), a hypertensive disorder specific to human pregnancy, remains a major cause of maternal mortality and morbidity globally. Endothelin-1 (ET-1) is a powerful vasoconstrictor that plays a crucial role in endothelial cell dysfunction, a characteristic feature of preeclampsia development. As a result, this study assessed the role of ET-1 in an HIV-infected preeclamptic cohort. Ethics approval was obtained BCA/17. Method: The study population (n = 72) was grouped according to pregnancy type i.e., normotensive (n = 36) and preeclamptic (n = 36) further stratified by human immunodeficiency virus (HIV) status. ET-1 levels were quantified using the Bioplex Immunoassay. Results: Gravidity, gestational age, systolic and diastolic blood pressure were significant across the study groups (p < 0.05). The concentration of ET-1 was significantly elevated in preeclamptic vs normotensive pregnancies regardless of HIV status (p ≤ 0.0418). Conclusion: This study observed a non-significant increase in ET-1 in the HIV positive preeclampsia group compared to the HIV negative pre-eclampsia group. ET-1 was significantly increased in pre-eclampsia compared to normotensive pregnancy. Isendlalelo nesingeniso: I-preeclampsia (PE), isifo sokunyuka kokugijima kwegazi esihlasela umuntu wesifazane ngesikhathi ekhulelwa, iyimbangela enkulu yokushona kukamama kanye nokugula komzimba emhlabeni wonke jikelele. I-Endothelin-1 (ET-1) iyi-vasoconstrictor enamandla ebamba iqhaza elibalulekile ekungasebenzi kahle kwamaseli we-endothelial, ibuye ibe nomthelela ekuthuthukeni kwe Preeclampsia. Lolu cwaningo beluhlola iqhaza le-ET-1 kubantu besifazane abanegciwane lesandulela ngculaza Kanye ne Preeclampsia ngesikhathi esisodwa. Indlela yokwenza: Inani labantu abacwaninguyo lingama-72, lihlukaniswa ngokwamaqembu ezinhlobo zokukhulelwa i.e., i-Abangenaso isifo (Normatensive) abangama-36 kanye nabanesifo se Pre-eclampsia abangama-36-, abuye aphindwa yahlukaniswa ngesimo seegciwane lesandulela ngculaza. Amazinga we-ET-1 asehlaziywa ngokusebenzisa iBioplex Immunoassay. Imiphumela: Ukuthola amandla wobudala, iminyaka yokuthomba, umfutho wegazi ne-diastolic kubonakale kwenza umehluko kuwo amaqembu ocwaningo (p < 0.05). Amazinga we-ET-1 akhuphuke kakhulu ekukhulelweni kwe-PE uma kuqhathaniswa nokukhulelwa okujwayelekile kungakhathalekile ukuthi sinjani isimo segciwane lesandulelaNgculaza (p ≤ 0.0418). Isiphetho: Lolu cwaningo lubone ukwanda okungabalulekanga kwe-ET-1 eqenjini labanepreeclampsia Kanye negciwane lesandulela ngculaza kuqhathaniswa nabane Preeclampsiankodwa bengenalo igciwane lesandulela ngculaza. I-ET-1 ibonakale yanda kakhulu ekukhuliseni i-preeclampsia uma kuqhathaniswa nokukhulelwa okujwayelekile. ItemHepatocyte growth factor and epidermal growth factor in HIV associated preeclampsia.(2018) Kupsamy, Kyle.; Naicker, Thajasvarie.Background: The survival or death of a cell is reliant upon growth factors. Hepatocyte and Epidermal Growth Factor (HGF and EGF) promote vital cellular processes such as cell survival, proliferation, differentiation, growth, invasion and repair via various pathways. Hence these growth factors facilitate normal pregnancy. In complications such as preeclampsia (PE), decreased trophoblast invasion results in defective spiral artery remodeling, which leads to decreased blood flow and a hypoxic micro-environment. In South Africa (SA), HIV infection and PE are the leading causes of maternal mortality and morbidity. In light of the high prevalence of HIV infection and PE in SA, this study aimed to determine the concentrations of HGF and EGF in HIV associated PE. Methods: Post ethics approval, serum samples were collected from normotensive HIV-negative (n = 20); normotensive HIV-positive (n = 20); preeclamptic HIV-negative (n = 20) and preeclamptic HIV-positive (n = 20) women. All HIV-positive women received Highly Active Anti-Retroviral Treatment (HAART). Quantification and analysis of HGF and EGF expression was attained by using the Bio-Plex multiplex immunoassay technique. Results: As expected there was a statistically significant difference between gestational age, systolic and diastolic blood pressures across the study groups (p<0.0001). No significant difference was noted in maternal age (p=0.16), parity (p=0.47) and maternal weight (p=0.36) across all study groups. Irrespective of pregnancy type, HGF was significantly increased in HIV-positive women vs HIV-negative women (p=0.0225). However, no statistical significance was found based on pregnancy type (p=0.8890). A significant decrease of HGF expression was noted between normotensive HIV-negative and normotensive HIV-positive women (p=0.0022). Irrespective of pregnancy type, EGF was found to be significantly elevated in HIV-positive compared to HIV-negative women (p=0.0055). In addition, preeclamptic women displayed a higher EGF level compared to normotensive women (p=0.003), regardless of HIV status. The Epidermal Growth Factor was significantly down-regulated in normotensive HIV-negative group vs normotensive HIV-positive (p<0.001), preeclamptic HIV-positive (p<0.001) and preeclamptic HIV-negative groups (p<0.001). Conclusion This novel study displays a significant up-regulation in the expression of HGF and EGF in HIV infection during pregnancy, reflecting an immune reconstitution following HAART. These findings may be caused due to the HIV accessory protein Tat that inhibits growth factor function thereby, negatively impacting cell migration. The up-regulation of EGF expression in PE, may be responsible for impaired trophoblast cell invasion. As anticipated in HIV associated PE, EGF expression increased in HIV infected pregnancies and PE. The expression Epidermal Growth Factor in HIV associated PE, may be used as a risk indicator, predicting PE development prior to the manifestations of clinical signs and symptoms. ItemThe role of c-jun n-terminal kinase (JNK) and tumour protein (p53) in HIV associated pre-eclampsia.(2017) Pillay, Yazira.; Naicker, Thajasvarie.Background: In pre-eclampsia, immune maladaptation to the foetal allograft results in impaired trophoblast invasion and defective spiral arterial remodelling with consequential placental oxidative stress. Placental apoptosis can be initiated by various stimuli including hypoxia and oxidative stress and is notably exaggerated in pre-eclampsia. This elevated apoptosis prevents normal replenishment of the syncytiotrophoblast, promotes syncytial degeneration and releases vasoactive or inflammatory factors into the maternal circulation thereby provoking the endothelial dysfunction seen in pre-eclampsia. Since the p53 antigen and JNK are important mediators of apoptosis we determined their expression in HIV associated pre-eclampsia. Method: Blood samples were collected from normotensive pregnant and pre-eclamptic HIV infected and negative women. Buffy coat was extracted and a Bio-plex multiplex assay to quantify expression of phosphorylated-p53 and JNK. Results: Based on pregnancy type, a significant difference in the expression of p53 was noted between the pre-eclamptic vs normotensive pregnant group regardless of HIV status (p=0.0162). Irrespective of pregnancy type, there was also a significant difference found between the HIV positive and HIV negative groups (p=0.0469). Furthermore, there was a significant difference in the expression of p53 between the HIV negative pre-eclamptic vs the HIV negative normotensive group and HIV infected normotensive vs the HIV negative pre-eclamptic group. Despite having no statistical significance (p=0.8701), the expression of JNK was found to be increased in the pre-eclamptic compared to the normotensive pregnant group. Similarly, based on HIV status, regardless of pregnancy type no statistical significance was found (p=0.2227), however, there was a decrease in the expression of JNK in the HIV positive compared to the HIV negative group. xiii Conclusion: These experiments demonstrate a significant increase in the expression of p53 with an upwards trend in the expression of JNK in pre-eclampsia, confirming their influence on trophoblast cell invasion in pre-eclampsia development. This increase in expression of p53 and JNK in pre-eclampsia, holds potential value as a risk indicator of pre-eclamptic development. In contrast, a significant down regulation of p53 with a downwards trend of JNK expression was noted in the HIV positive group, possibly due to immune reconstitution following HAART. ItemExpression of plasma nuclear factor KAPPA-B (NFκB) and inhibitory subunit KAPPA B ALPHA (IκB-α) in HIV-associated pre-eclamsia.(2017) Zozo, Bambanani Selunathi.; Naicker, Thajasvarie.Objective: The relationship between pre-eclampsia and HIV-1 infection is one of the most unexplored relationships in research. Pre-eclampsia is characterized by inflammation and HIV is characterized by a decline in immune activity. The NFκB pathway is involved in pre-eclampsia and in HIV-1 infection as a transcriptional factor in both conditions. Previous literature has showed that NFκB is upregulated in both pre-eclampsia and HIV-1 infection. Therefore, the aim of this study was to investigate the level of plasma NFκB and the inhibitory subunit IκB-α in HIV associated pre-eclampsia. Method: This retrospective study examined plasma NFκB and IκB-α expression in normotensive (n =32) and preeclamptic (n = 34) HIV positive and HIV negative pregnant women. Quantification of plasma NFκB and IκB-α expression were done using a Bio-Plex Multiplex immunoassay. Results: Our results demonstrated a significant decrease in the level of plasma NFκB expression in pre-eclamptic compared to normotensive pregnancies (p< 0.05), irrespective of HIV status. However, the level of plasma NFκB expression was not significantly different between HIV positive and HIV negative women, irrespective of pregnancy type. Moreover, a significant difference in NFκB expression across all the study groups was observed, specifically a significant decrease in NFκB expression in HIV positive pre-eclamptic women compared to normotensive women (p < 0.05). Furthermore, based on pregnancy type, a significant decrease in the level of plasma IκB-α expression was noted in pre-eclamptic compared to normotensive pregnancies, irrespective of HIV status (p< 0.05). However, our results showed no significant difference across all groups. Although no significance was xii observed, a downwards trend in plasma IκB-α expression was observed in HIV positive pre-eclamptic compared to normotensive women. Conclusion: Our study demonstrates decreased plasma NFκB and IκB-α expression in preeclamptic women irrespective of HIV status. This could be attributed to oxidative stress as an underlying factor subsequently leading to decreased plasma NFκB and IκB-α in preeclamptic women. HIV status had no effect on Plasma NFκB and IκB-α expression. The similarity in plasma NFκB and IκB-α expression based on HIV status may be due to antiretroviral therapy. ItemThe role of albumin, β₂M and Cystatin C as urinary biomarkers in idopathic and HIV-associated focal segmental glomerulosclerosis in children.(2017) Persadh, Kalindi.; Naicker, Thajasvarie.; Bhimma, Rajendra.Abstract available in PDF file. ItemThe role of C- reactive protein and serum amyloid A in HIV associated pre-eclampsia.(2018) Sikutshwa, Akhona.; Naicker, Thajasvarie.Abstract available in PDF file. ItemCell signaling expression of stat-3 and mek-1 in HIV-associated pre-eclampsia.(2017) Padayachee, Sayuri.; Naicker, Thajasvarie.Background: Sub-Saharan Africa remains the epicenter of the HIV pandemic. In South Africa 35.8% of maternal deaths are ascribed to non-pregnancy related infections, namely HIV infection. The prevalence rate of HIV in pregnancy in KwaZulu-Natal is an estimated 37.7%. Furthermore, in women of reproductive age, the incidence of HIV infection is high (18.8%). The shallow trophoblast invasion and the lack of physiological conversion of the spiral arteries into small bore low resistance conduits is the primary cause behind the pathogenesis of pre-eclampsia. HIV-positive patients on HAART are predisposed to pre-eclampsia development. Trophoblast cells are stimulated to invade the maternal decidua by interacting cytokines and growth factors in the local environment through signal transduction pathways. Aberrant cell signaling and signaling molecule function impedes trophoblast invasion necessary for a healthy pregnancy, leading to endothelial dysfunction. As a result, the expression of cell signaling analytes may potentially be a predictive biomarker for patients at risk to pre-eclamptic development. This study investigated expression of STAT-3 and MEK-1 in HIV-associated pre-eclampsia, as a diagnostic tool of abnormal placentation in pre-eclampsia. Method: Venous blood samples of 40 normotensive and 40 pre-eclamptic patients further stratified by HIV status were collected at a large regional hospital for buffy coat extraction, followed by analysis of cell signalling analytes by the Bio-Plex Multiplex immunoassay. Results: The downregulation of both STAT-3 and MEK-1 expression was observed in pre-eclamptic pregnancies irrespective of HIV status, respectively (p < 0.05; p = 0.1526). No significance for STAT-3 (p = 0.0859) was detected between HIV-positive and HIV-negative groups irrespective of pregnancy type, although a lowered trend was observed in the HIV-positive group. Contrary to expected outcomes, MEK-1 expression was significantly decreased (p = 0.0102) in the HIV-positive group, irrespective of pregnancy type. Conclusion: This study demonstrated the downregulation of STAT-3 and MEK-1 expression in pre-eclampsia, corroborating a defective trophoblast invasion. The decreased expression of STAT-3 in HIV-infection may be attributed to HAART and/or to the reduced expression of IL-6 that stimulates STAT-3 phosphorylation. It is also plausible to assume that the downregulation of MEK-1 arises from non-phosphorylation of HIV-regulatory proteins. Additional studies, are required to further investigate the role of signal transduction pathways and its effect on HAART in pre-eclampsia development. ItemTrace element analysis of biological samples from normotensive and pre-eclamptic South African pregnant women.(2016) Soobramoney, Cassandra.; Naicker, Thajasvarie.; Maduray, Kaminee.; Moodley, Jagidesa.Abstract available in PDF file. ItemThe role of pro-renin and its receptor expression in pre-eclampsia complicated by HIV infection.(2016) Silwane, Londiwe N. B.; Naicker, Thajasvarie.; Ajith, Anushka.Abstract available in PDF file. ItemThe role of CD69 in HIV-associated pre-eclamptic and normotensive pregnant black South Africans.(2016) Zulu, Nomfundo Nokuthula Simlindile.; Ajith, Anushka.; Naicker, Thajasvarie.; Moodley, Jagidesa.Abstract available in PDF file. ItemRole of biomakers, kidney injury molecule-1, interleukin-18, calbindin and monocyte chemotactic protein-1, in evaluating and diagnosing kidney injuyr in pre-eclampsia.(2016) Eltounali, Soumaya.; Naicker, Thajasvarie.Abstract available in PDF file.