Abstract:R.M.B. has received speaking fees and research grants from Alexion Pharmaceuticals. Alexion Pharmaceuticals was not involved with this work in any manner. B.B.F. reports no conflict of interest.
“…[ 6 ]), Alzheimer disease [ 36 ], bullous pemphigoid [ 37 ] and pregnancy-related disorders (see below and Ref. [ 38 • ]). Figure 2 Disease-associated CD46 mutations.…”
Section: Deficiency Statesmentioning
confidence: 99%
“…CD46 mutated proteins have also been implicated in the pathophysiology of other disorders. For example, studies have evaluated the MCP gene in the pregnancy-related disorder: pre-eclampsia (PE), especially the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome (reviewed by Burwick and Feinberg [ 38 • ] and Salmon et al [ 49 ]). PE is a devastating multi-system disorder that occurs in 3–5% of pregnancies accounting for significant neonatal morbidity and mortality.…”
Section: Deficiency Statesmentioning
confidence: 99%
“…MCP mutations were identified in ∼8% of cases, although the range varied between 0–12% (summarized in Ref. [ 38 • ]). Similar to HUS, the precise etiology is unknown but likely relates (at least in part) to endothelial cell dysfunction secondary to excessive complement activation.…”
“…[ 6 ]), Alzheimer disease [ 36 ], bullous pemphigoid [ 37 ] and pregnancy-related disorders (see below and Ref. [ 38 • ]). Figure 2 Disease-associated CD46 mutations.…”
Section: Deficiency Statesmentioning
confidence: 99%
“…CD46 mutated proteins have also been implicated in the pathophysiology of other disorders. For example, studies have evaluated the MCP gene in the pregnancy-related disorder: pre-eclampsia (PE), especially the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome (reviewed by Burwick and Feinberg [ 38 • ] and Salmon et al [ 49 ]). PE is a devastating multi-system disorder that occurs in 3–5% of pregnancies accounting for significant neonatal morbidity and mortality.…”
Section: Deficiency Statesmentioning
confidence: 99%
“…MCP mutations were identified in ∼8% of cases, although the range varied between 0–12% (summarized in Ref. [ 38 • ]). Similar to HUS, the precise etiology is unknown but likely relates (at least in part) to endothelial cell dysfunction secondary to excessive complement activation.…”
“…In a healthy pregnancy, several immunological adaptations support immunologic tolerance to the semi-allogenic foetus and placenta and simultaneously protects the mother and foetus against pathogens [20]. The inhibitory action of maternal immune cells to paternal antigens in the developing foetus is key to a successful pregnancy.…”
Section: Immune Response and The Complement Systemmentioning
Introduction: This review explores angiogenesis, vascular dysfunction, the complement system, RAAS, apoptosis and NETosis as potential pathways that are dysregulated during preeclampsia, HIV infection and ART usage. Results: HIV-1 accessory and matrix proteins are protagonists for the elevation of oxidative stress, apoptosis, angiogenesis, and elevation of adhesion markers. Despite the immunodeficiency during HIV-1 infection, HIV-1 exploits our cellular defence arsenal by escaping cell-mediated lysis, yet HIV-1 infectivity is enhanced via C5a release of TNF-α and IL-6. This review demonstrates that PE is an oxidatively stressed microenvironment associated with increased apoptosis and NETosis, but with a decline in angiogenesis. Immune reconstitution in the duality of HIV-1 and PE by protease inhibitors, HAART and nucleoside reverse transcriptase, affect similar cellular pathways that eventuate in loss of endothelial cell integrity and, hence, its dysfunction. Conclusions: HIV-1 infection, preeclampsia and ARTs differentially affect endothelial cell function. In the synergy of both conditions, endothelial dysfunction predominates. This knowledge will help us to understand the effect of HIV infection and ART on immune reconstitution in preeclampsia.
“…Research that identifies which patients are at the highest risk of immediate adverse outcomes is an important first step to better triaging and transitioning follow-up care in the early postpartum period. Clinical interventions presented during the workshop with the potential to improve preeclampsia outcomes include the use of diuretics, complement inhibition, 42 statins, 43 targeted blood pressure maintenance, 44 and postpartum angiotensin-converting enzyme inhibitors. Investigating such novel management strategies will require both funding and support for conducting research in pregnant and lactating people.…”
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