AUTHOR=Balduit Andrea , Agostinis Chiara , Mangogna Alessandro , Zito Gabriella , Stampalija Tamara , Ricci Giuseppe , Bulla Roberta 

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

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1419540

DOI=10.3389/fimmu.2024.1419540

ISSN=1664-3224

ABSTRACT=<p>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 (<italic>i.e.</italic>, 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.</p><sec><title>Systematic review registration</title><p><uri xlink:href="https://www.crd.york.ac.uk/prospero/" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.crd.york.ac.uk/prospero/</uri>, identifier CRD42024503070.</p></sec>