Plasma E‐selectin and kallistatin as predictive markers of histologic chorioamnionitis in women with preterm premature rupture of membranes

Abstract

Problem:We aimed to assess the predictive potential of 12 plasma biomarkers to predict acute histologic chorioamnionitis (HCA) in women with preterm premature rupture of membranes (PPROM) and to develop multi-biomarker panels based on these biomarkers in combination with widely used conventional laboratory markers. Method of study:This was a retrospective cohort study involving 81 singleton pregnant women (24-34 weeks of gestation) who delivered within 96 h of blood sampling.White blood cell (WBC) count, differential counts, and C-reactive protein (CRP) levels were measured at admission. The levels of DKK-3, Fas, haptoglobin, IGFBP-2, kallistatin, MIP-1α, MMP-2, MMP-8, pentraxin 3, progranulin, E-selectin, and P-selectin were evaluated by ELISA using stored plasma samples. The primary outcome measure was acute HCA.Results: Multivariate analyses showed that low plasma E-selectin and kallistatin levels were independently associated with HCA occurrence after adjusting for gestational age. Using a stepwise regression analysis, a multi-biomarker panel comprising plasma E-selectin, serum CRP, and WBC was developed, which provided a good prediction of acute HCA in women with PPROM (area under the curve [AUC], 0.899), with a significantly higher AUC than that of any single variable included in the panel (P < 0.05).The plasma levels of DKK-3, Fas, haptoglobin, IGFBP-2, MIP-1α, MMP-2, MMP-8, pentraxin 3, and P-selectin were not significantly associated with HCA occurrence.Conclusions: This study identified E-selectin and kallistatin as potential plasma biomarkers associated with acute HCA in women with PPROM. Their combined analysis with serum CRP and WBC counts significantly improved acute HCA diagnosis.

Plasma IGFBP‐1, Fas, kallistatin, and P‐selectin as predictive biomarkers of histologic chorioamnionitis and associated intra‐amniotic infection in women with preterm labor

“…23,[63][64][65][66] In the context of PPROM, shotgun proteomics of pooled AF samples showed that kallistatin expression is significantly downregulated in women with PPROM complicated with both HCA and MIAC compared with those without these conditions 67 Similarly, in a recent study, we showed that kallistatin levels are significantly decreased in the plasma of patients with acute HCA in the context of PPROM. 68 In line with previous studies, 23,[63][64][65]67 we demonstrated herein that decreased plasma kallistatin levels are independently associated with microbial-associated HCA in PTL patients.…”

“…In particular, kallistatin acts as a negative acute‐phase protein, which is rapidly reduced after lipopolysaccharide‐induced inflammation, 62 and thus its levels in plasma tend to decrease in several inflammatory diseases, such as inflammatory bowel disease, septic syndrome, severe pneumonia, and obesity 23,63–66 . In the context of PPROM, shotgun proteomics of pooled AF samples showed that kallistatin expression is significantly downregulated in women with PPROM complicated with both HCA and MIAC compared with those without these conditions 67 Similarly, in a recent study, we showed that kallistatin levels are significantly decreased in the plasma of patients with acute HCA in the context of PPROM 68 . In line with previous studies, 23,63–65,67 we demonstrated herein that decreased plasma kallistatin levels are independently associated with microbial‐associated HCA in PTL patients.…”

Expression of inflammatory, angiogenic, and extracellular matrix‐related mediators in the cervicovaginal fluid of women with preterm premature rupture of membranes: Relationship with acute histological chorioamnionitis

“…Therefore, it is of particular clinical importance to identify patients with PPROM complicated by microbial‐associated HCA, preferably based on non‐invasive biomarkers, to allow tailoring suitable and timely treatment strategies. In a previous study, we reported that low plasma levels of E‐selectin, and maternal C‐reactive protein levels and white blood cell counts could be used as independent biomarkers for microbial‐associated HCA in pregnancies complicated PPROM 53 . Herein, we further demonstrated that elevated CVF levels of IL‐6, IL‐8, M‐CSF, MMP‐8, and TNFR2 are also independently associated with microbial‐associated HCA.…”

“…Further sufficiently powered prospective studies are needed to confirm our observations and to elucidate the possible mechanisms by which HCA and associated infection/inflammation affect the levels of these proteins in the CVF of patients with PPROM. In addition, whether these newly identified CVF‐based biomarkers can contribute for predicting PPROM‐associated acute HCA when used in combination with other currently available tests/biomarkers (e.g., C‐reactive protein, E‐selectin, kallistatin, MMP‐9, IL‐6, IGFBP‐1, and S100 A8/A9 in the blood) should be addressed in future investigations 36,53 …”

“…In addition, whether these newly identified CVF-based biomarkers can contribute for predicting PPROM-associated acute HCA when used in combination with other currently available tests/biomarkers (e.g., C-reactive protein, Eselectin, kallistatin, MMP-9, IL-6, IGFBP-1, and S100 A8/A9 in the blood) should be addressed in future investigations. 36,53…”