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Evaluation of leucine-rich alpha-2 glycoprotein as a biomarker of fetal infection.

ABSTRACT: This study aimed to determine the association between umbilical cord leucine-rich alpha-2 glycoprotein (LRG) and fetal infection and investigate the underlying mechanism of LRG elevation in fetuses. We retrospectively reviewed the medical records of patients who delivered at Osaka University Hospital between 2012 and 2017 and selected those with histologically confirmed chorioamnionitis (CAM), which is a common pregnancy complication that may cause neonatal infection. The participants were divided into two groups: CAM with fetal infection (CAM-f[+] group, n = 14) and CAM without fetal infection (CAM-f[-] group, n = 31). Fetal infection was defined by the histological evidence of funisitis. We also selected 50 cases without clinical signs of CAM to serve as the control. LRG concentrations in sera obtained from the umbilical cord were unaffected by gestational age at delivery, neonatal birth weight, nor the presence of noninfectious obstetric complications (all, p > 0.05). Meanwhile, the LRG levels (median, Interquartile range [IQR]) were significantly higher in the CAM-f(+) group (10.37 [5.21-13.7] ?g/ml) than in the CAM-f(-) (3.61 [2.71-4.65] ?g/ml) or control group (3.39 [2.81-3.93] ?g/ml; p < 0.01). The area under the receiver operating characteristic (ROC) curve of LRG for recognizing fetal infection was 0.92 (optimal cutoff, 5.08 ?g/ml; sensitivity, 86%; specificity, 88%). In a mouse CAM model established by lipopolysaccharide administration, the fetal LRG protein in sera and LRG mRNA in the liver were significantly higher than those in phosphate-buffered saline (PBS)-administered control mice (p < 0.01). In vitro experiments using a fetal liver-derived cell line (WRL68) showed that the expression of LRG mRNA was significantly increased after interleukin (IL)-6, IL-1?, and tumor necrosis factor- alpha (TNF-?) stimulation (p < 0.01); the induction was considerably stronger following IL-6 and TNF-? stimulation (p < 0.01). In conclusion, LRG is an effective biomarker of fetal infection, and fetal hepatocytes stimulated with inflammatory cytokines may be the primary source of LRG production in utero.

SUBMITTER: Kajimoto E

PROVIDER: S-EPMC7676652 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Evaluation of leucine-rich alpha-2 glycoprotein as a biomarker of fetal infection.

Kajimoto Etsuko E Endo Masayuki M Fujimoto Minoru M Matsuzaki Shinya S Fujii Makoto M Yagi Kazunobu K Kakigano Aiko A Mimura Kazuya K Tomimatsu Takuji T Serada Satoshi S Takeuchi Makoto M Yoshino Kiyoshi K Ueda Yutaka Y Kimura Tadashi T Naka Tetsuji T

PloS one 20201119 11

This study aimed to determine the association between umbilical cord leucine-rich alpha-2 glycoprotein (LRG) and fetal infection and investigate the underlying mechanism of LRG elevation in fetuses. We retrospectively reviewed the medical records of patients who delivered at Osaka University Hospital between 2012 and 2017 and selected those with histologically confirmed chorioamnionitis (CAM), which is a common pregnancy complication that may cause neonatal infection. The participants were divid ...[more]

PMID: 33211747

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Project description:The aim of this study is to evaluate the diagnostic accuracy of leucine-rich α-2-glycoprotein 1 (LRG1) in saliva as a novel biomarker for acute appendicitis in the pediatric population. From October 2021 to June 2022, 92 children aged 5 to 17 years who presented with acute abdomen and suspected acute appendicitis were enrolled in this prospective study. The parameters documented included demographic and clinical information, as well as operative and postoperative data. Patients were divided into two groups: those with acute appendicitis who underwent laparoscopic appendectomy (n = 46) and those without appendicitis (n = 46). The total white blood cell (WBC) count, percent of neutrophils, C-reactive protein (CRP) level, and salivary LRG1 were compared between groups. A commercially available enzyme-linked immunosorbent assay (ELISA) LRG kit was used to measure the LRG levels. The median salivary LRG1 level was significantly higher in the group of children with pathohistologically confirmed acute appendicitis compared to the control group: 233.45 ng/mL (IQR 114.9, 531.2) vs. 55.95 ng/mL (IQR 51.5, 117.9), p < 0.001. LRG1 had an overall good receiver-operator characteristic area under the curve of 0.85 (95% CI 0.76-0.92; p < 0.001). The optimal LRG1 cutoff with best separation between acute appendicitis and the controls was >352.6 ng/mL (95% CI from >270.7 to >352.6). Although the specificity was 100% at this cutoff, the sensitivity for identifying appendicitis was 36%. In addition, a significant difference was found between groups in the laboratory values of all inflammatory markers tested: WBC, absolute neutrophil count, and CRP (p < 0.001 for all). Although LRG1 in saliva showed a good AUC parameter and significantly higher values in patients with acute appendicitis compared to the controls, its usefulness in the patient population who present at emergency departments with abdominal pain is debatable. Future studies should focus on investigating its diagnostic potential.

Dataset Information

Evaluation of leucine-rich alpha-2 glycoprotein as a biomarker of fetal infection.

Publications

Evaluation of leucine-rich alpha-2 glycoprotein as a biomarker of fetal infection.

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