The role of immunoglobulin isotypes (IgG1-IgG4, IgA AND IgM) in HIV preeclamptics on highly active anti-retroviral therapy, in South Africa.

Abstract

Background: The epicentre of a successful pregnancy lies within the placenta and is nurtured by suppressed immune responses. However, the fragile balance between maternal inflammatory responses and the regulation of maternal immunoglobulins is distorted by HIV and Preeclampsia (PE). Preeclampsia and co-morbid diseases such as HIV infections are major contributors to maternal morbidity and mortality, worldwide. Furthermore, the effects of Highly Active Antiretroviral therapy (HAART) on the reconstitution of immunity in HIV preeclamptics remain obscure. Therefore, the current study aims to investigate the role of immunoglobulins in HIV infected preeclamptics and elucidate the effects of HAART on immunoglobulin levels in HIV infected PE. Method: Ethical clearance was granted by the Biomedical Research Ethics Committee (BREC). Serum samples of 38 normotensive and 38 preeclamptic pregnancies were collected at a regional hospital and further categorized based on HIV status. The serum samples were then subjected to the analysis of immunoglobulin (IgG1-IgG4, IgA and IgM) concentration (ng/dl). The Bio-Plex immunoassay technique of analysis was used to investigate the concentration of immunoglobulin isotypes in the sample population. Immunoglobulin concentrations were considered significant when p < 0.05. Results: Immunoglobulin concentration was evaluated in pregnancy type irrespective of HIV status. A non-significant down-regulated trend of IgG1, IgG3 and IgG4 was observed, whilst IgG2 and IgM showed a non-significant up-regulation. On the contrary, IgA levels presented a significant increase in preeclamptics irrespective of HIV status. However, in HIV infected pregnancies irrespective of pregnancy type IgG1 presented a non-significant up-regulated trend, whilst IgG3 and IgG4 showed non-significant down-regulatory trends. Nonetheless, IgG2, IgA and IgM demonstrated a significant down-regulation in HIV infected pregnancies, irrespective of pregnancy type. Furthermore, IgG1, IgG3, IgG4 and IgM showed a non-significant difference when analysed according to pregnancy type and HIV status. However, IgG2 and IgA presented a significant up-regulation in HIV negative PE. Conclusion: This study highlights the importance of the maternal-fetal transfer of immunoglobulins (IgG subclass) in pregnancy. We report a significant up-regulation of IgG2, indicating its role in activating the classical complement pathway thereby, exacerbating the inflammatory response in PE. The up-regulation of IgA is an ingenerate anti-inflammatory response, which inhibits the exacerbated inflammatory cascade via classical complement activation in PE. In HIV infection the down-regulation of IgG2, IgA and IgM maybe due to HAART. In addition, IgA showed an up-regulation in HIV associated PE, suggesting that the reconstitution of HAART is insufficient in neutralizing the exaggerated inflammatory response in PE. To further understand the role of IgG2 and IgA in HIV associated PE, larger studies are warranted.