The function of Adipsin and C9 protein in the complement system in HIV-associated preeclampsia.

Abstract

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.