The complement system in preeclampsia: a review of its activation and endothelial injury in the triad of COVID-19 infection and HIV-associated preeclampsia

David, Mikyle; Naicker, Thajasvarie

doi:10.5468/ogs.22175

Cited by 3 publications

(2 citation statements)

References 139 publications

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“…There may have been a tendency Seyoung Kim, et al Incidence of mild and severe preeclampsia toward overreporting by physicians, and misclassification or miscoding may have affected the results of this study. Given that the incidence of mild PE was reported to be 2.5-4 times higher than that of severe PE in prior studies [18][19][20], we believe that the possibility of misclassification would have been minimal. Second, our operative definition of severe PE based on the prescription of MgSO 4 may have been affected by the recommendation of the United States.…”

Section: Discussionmentioning

confidence: 76%

Differential trend of mild and severe preeclampsia among nulliparous women: a population-based study of South Korea

Kim,

Lee,

Kim

et al. 2023

Obstet Gynecol Sci

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We explored the annual risks of mild and severe preeclampsia (PE) among nulliparous women. Using the National Health Information Database of South Korea, 1,317,944 nulliparous women who gave live births were identified. Mild PE increased from 0.9% in 2010 to 1.4% in 2019 (P for trend=0.006), while severe PE decreased from 0.4% in 2010 to 0.3% in 2019 (P=0.049). The incidence of all types of PE (mild and severe) showed no linear change (P=0.514). Adjusted odds ratio (OR) of severe PE decreased in 2013 (0.68; 95% confidence interval [CI]: 0.60, 0.77) and beyond compared to that in 2010, while the OR of mild PE increased in 2017 (1.14; 95% CI: 1.06, 1.22) and beyond. Mild PE was found to be less likely to progress to the severe form since 2010; however, the overall risk of PE among women did not change.

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Section: Discussionmentioning

confidence: 76%

Differential trend of mild and severe preeclampsia among nulliparous women: a population-based study of South Korea

Kim,

Lee,

Kim

et al. 2023

Obstet Gynecol Sci

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“…Even though C dysregulation may have a role in affecting placental formation before the disease onset, the contribution of C in PE pathophysiology mainly consists in a secondary mechanism of amplification of tissue injury and inflammation, following endothelial damage and local placental ischemia and hypoxia, and results in a cascade of reactions that contribute to the rapid development and symptom exacerbation of PE at the systemic level ( 69 , 70 ). When discussing C testing, one should always bear in mind the complexity of C and the interdependence among its individual components.…”

Section: Discussionmentioning

confidence: 99%

Systematic review of the complement components as potential biomarkers of pre-eclampsia: pitfalls and opportunities

Balduit,

Agostinis,

Mangogna

et al. 2024

Front. Immunol.

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The complement system (C) is a crucial component of the innate immune system. An increasing body of research has progressively shed light on the pivotal role of C in immunological tolerance at the feto-maternal interface. Excessive C activation or impaired C regulation may determine the onset of pregnancy-related pathological conditions, including pre-eclampsia (PE). Thus, several studies have investigated the presence of C components or split products in blood matrixes (i.e., plasma, serum), urine, and amniotic fluid in PE. In the current study, we systematically reviewed the currently available scientific literature reporting measurements of C components as circulating biomarkers in PE, based on a literature search using Pubmed, Scopus, and Embase databases. A total of 41 out of 456 studies were selected after full-text analysis. Fourteen studies (34.1%) were identified as measuring the blood concentrations of the classical pathway, 5 (12.1%) for the lectin pathway, 28 (68.3%) for the alternative pathway, 17 (41.5%) for the terminal pathway components, and 16 (39%) for C regulators. Retrieved results consistently reported C4, C3, and factor H reduction, and increased circulating levels of C4d, Bb, factor D, C3a, C5a, and C5b-9 in PE compared to normal pregnancies, depicting an overall scenario of excessive C activation and aberrant C regulation. With evidence of C activation and dysregulation, C-targeted therapy is an intriguing perspective in PE management. Moreover, we also discussed emerging pitfalls in C analysis, mainly due to a lack of experimental uniformity and biased cohort selection among different studies and laboratories, aiming to raise a more comprehensive awareness for future standardization.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024503070.

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Differential expression of the angiotensin receptors (AT1, AT2, and AT4) in the placental bed of HIV-infected preeclamptic women of African ancestry

2023

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The Renin-Angiotensin-Aldosterone System (RAAS) is implicated in the pathophysiology of preeclampsia (PE). There is a paucity of data on uteroplacental angiotensin receptors AT1-2 and 4. We evaluated the immunoexpression of AT1R, AT2R, and AT4R within the placental bed of PE vs. normotensive (N) pregnancies stratified by HIV status. Placental bed (PB) biopsies (n = 180) were obtained from N and PE women. Both groups were stratified by HIV status and gestational age into early-and late onset-PE. Immuno-labeling of AT1R, AT2R, and AT4R was quantified using morphometric image analysis. Immunostaining of PB endothelial cells (EC) and smooth muscle cells of spiral arteries (VSMC) displayed an upregulation of AT1R expression compared to the N group (p < 0.0001). Downregulation of AT2R and AT4R expression was observed in PE vs. N group (p = 0.0042 and p < 0.0001), respectively. AT2R immunoexpression declined between HIV+ve and HIV−ve groups, while AT1R and AT4R displayed an increase. An increase in AT1R expression was noted in the EOPE−ve/+ve and LOPE−ve/+ve compared to N−ve/N+ve. In contrast, AT2R and AT4R expression decreased in EOPE−ve/+ve and LOPE-ve/+ve compared to N−ve/N+ve. We demonstrate a significant downregulation of AT2R and AT4R with a concomitant elevated AT1R immunoexpression within PB of HIV-infected PE women. In addition, a decline in AT2R and AT4R with an increase in AT1R immunoexpression in PE, EOPE, and LOPE vs. normotensive pregnancies, irrespective of HIV status. Thus highlighting differential immunoexpression of uteroplacental RAAS receptors based on pregnancy type, HIV status, and gestational age.

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The complement system in preeclampsia: a review of its activation and endothelial injury in the triad of COVID-19 infection and HIV-associated preeclampsia

Cited by 3 publications

References 139 publications

Differential trend of mild and severe preeclampsia among nulliparous women: a population-based study of South Korea

Differential trend of mild and severe preeclampsia among nulliparous women: a population-based study of South Korea

Systematic review of the complement components as potential biomarkers of pre-eclampsia: pitfalls and opportunities

Differential expression of the angiotensin receptors (AT1, AT2, and AT4) in the placental bed of HIV-infected preeclamptic women of African ancestry

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