The role of complement components C2 and C5a in HIV associated preeclampsia.

Abstract

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.