Cervical Alpha-Actinin-4 Is Upregulated in Women with Threatened Preterm Labor and Microbial Invasion of the Amniotic Cavity

Abstract

Objective: To characterize the proteome profile of women with threatened preterm labor (PTL) below 34;0 weeks with and without microbial invasion of the amniotic cavity (MIAC) using mass spectrometry in the amniotic fluid (AF) and Western blot analysis in the cervical mucus and the vaginal fluid. Subjects and Methods: In the discovery phase, a case-control study including 8 women with MIAC and 7 without matched for gestational age at sampling was performed. Proteomic profile characterization was done using the LTQ VELOS Orbitrap mass spectrometer in the AF. In the validation phase, a selection of the proteins differentially expressed by mass spectrometry in the genital samples of a prospective cohort of 109 women was validated by Western blot analysis. Results: In the discovery phase, the mass spectrometry analysis identified a total of 444 proteins. Sixteen were chosen for validation, being involved in defense (calgranulin A, B, C, C-reactive protein), cytoskeletal remodeling (alpha-actinin-4 [ACTN-4], plastin-2, α2-antiplasmin, vitronectin), metabolism (cystatin-β, glucose 6 phosphate isomerase, glutathione S-transferase, prostaglandin D2 synthase, corticosteroid-binding globulin), and vascular (α1-antichymotrypsin, hemopexin, endosialin) pathways. In the validation phase, cervical ACTN-4 was the only significantly upregulated protein in women with MIAC with an odds ratio of 6.8 (p = 0.002). Conclusions: Cervical ACTN-4 was significantly upregulated in the group of women with PTL with MIAC.

Plasma Kallistatin and Progranulin as Predictive Biomarkers of Intraamniotic Inflammation, Microbial Invasion of the Amniotic Cavity, and Composite Neonatal Morbidity/Mortality in Women With Preterm Premature Rupture of Membranes

“…The precision and accuracy of the nine ELISAs were validated for plasma samples before use through spike‐and‐recovery and linearity‐of‐dilution experiments, which revealed their good performance. These proteins were selected to be explored in the present study because (i) they were previously suggested to be useful blood biomarkers for the detection of histologic inflammation in the placenta; however, whether their altered expression in the plasma is associated with AF inflammation/infection and adverse neonatal outcomes in the context of PPROM remains unclear [22, 23]; (ii) they could have potential clinical significance in the maternal blood regarding the outcomes of interest herein investigated, considering previous proteomic profiling studies that suggested that they could be potential candidates biomarkers for MIAC, IAI, or preterm birth [18, 24–26, 28, 32]; and because (iii) their related signaling pathways (such as inflammation/immune‐, cell adhesion, and ECM homeostasis [https://www.uniprot.org/]) are known to be involved in the pathogenesis of adverse pregnancy and neonatal outcomes [33–36].…”

Serum apolipoprotein A-II and alpha-2-antiplasmin levels in midtrimester can be used as predictors of preterm delivery

“… 8 Cervical α-actinin-4 increased in patients with preterm delivery. 9 However, none of these markers can predict premature delivery in the early stage of pregnancy. Therefore, this study aimed to identify serum markers that can predict preterm delivery at an earlier stage of pregnancy.…”