Jennifer B Fundora1, Jie Zhu2, Lisa R Yanek3, Mitzi Go4, Fauzia Shakeel4, Sandra S Brooks4, Jun Yang2, David J Hackam5, Allen D Everett2, Darla R Shores6. 1. Department of Pediatrics, Division of Neonatology, Johns Hopkins University School of Medicine, 1800 Orleans St, Suite 8534, Baltimore, MD, 21287, USA. jfundor1@jhmi.edu. 2. Department of Pediatrics, Division of Pediatric Cardiology, Johns Hopkins University School of Medicine, 720 Rutland Ave. Ross Building 1129, Baltimore, MD, 21205, USA. 3. Department of Medicine, Johns Hopkins University School of Medicine, 1830 E Monument St 1830 Building Suite 8024, Baltimore, MD, 21287, USA. 4. Division of Neonatology, Maternal, Fetal and Neonatal Institute, Johns Hopkins All Children's Hospital, 501 6th Ave S, St. Petersburg, FL, 33701, USA. 5. Department of Surgery, Division of Pediatric Surgery, Johns Hopkins University School of Medicine, 1800 Orleans St, Suite 7310, Baltimore, MD, 21287, USA. 6. Department of Pediatrics, Division of Pediatric Gastroenterology, Johns Hopkins University School of Medicine, 600 N Wolfe St, Baltimore, MD, 21287, USA.
Abstract
BACKGROUND: Neonates are at risk of gastrointestinal emergencies including necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP). Identifying biomarkers to aid in diagnosis is imperative. We hypothesized that circulating intestinal-specific protein concentrations would distinguish infants with intestinal injury from controls. AIMS: To identify serum concentrations of intestinal-specific protein(s) in infants with intestinal injury and controls. METHODS: We used an in silico approach to identify intestinal-specific proteins. We collected serum from control infants and infants with NEC or SIP and measured protein concentrations using ELISA. If baseline concentrations were near the detection limit in initial control assays, we proceeded to assess concentrations in a larger cohort of controls and infants with injury. Control infants were frequency matched to infants with injury and compared with nonparametric and mixed-effects models analysis. RESULTS: We evaluated four proteins with high intestinal expression: Galectin-4 (Gal-4), S100G, Trefoil Factor-3, and alanyl aminopeptidase. Only Gal-4 demonstrated consistent results near the lower limit of quantification in controls and was studied in the larger cohorts. Gal-4 concentration was low in 111 control infants (median 0.012 ng/ml). By contrast, Gal-4 was significantly increased at diagnosis in infants with surgical NEC and SIP (n = 14, p ≤ 0.001 and n = 8, p = 0.031) compared to matched controls, but not in infants with medical NEC (n = 32, p = 0.10). CONCLUSIONS: Of the intestinal-specific proteins evaluated, circulating Gal-4 concentrations were at the assay detection limit in control infants. Gal-4 concentrations were significantly elevated in infants with surgical NEC or SIP, suggesting that Gal-4 may serve as a biomarker for neonatal intestinal injury.
BACKGROUND: Neonates are at risk of gastrointestinal emergencies including necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP). Identifying biomarkers to aid in diagnosis is imperative. We hypothesized that circulating intestinal-specific protein concentrations would distinguish infants with intestinal injury from controls. AIMS: To identify serum concentrations of intestinal-specific protein(s) in infants with intestinal injury and controls. METHODS: We used an in silico approach to identify intestinal-specific proteins. We collected serum from control infants and infants with NEC or SIP and measured protein concentrations using ELISA. If baseline concentrations were near the detection limit in initial control assays, we proceeded to assess concentrations in a larger cohort of controls and infants with injury. Control infants were frequency matched to infants with injury and compared with nonparametric and mixed-effects models analysis. RESULTS: We evaluated four proteins with high intestinal expression: Galectin-4 (Gal-4), S100G, Trefoil Factor-3, and alanyl aminopeptidase. Only Gal-4 demonstrated consistent results near the lower limit of quantification in controls and was studied in the larger cohorts. Gal-4 concentration was low in 111 control infants (median 0.012 ng/ml). By contrast, Gal-4 was significantly increased at diagnosis in infants with surgical NEC and SIP (n = 14, p ≤ 0.001 and n = 8, p = 0.031) compared to matched controls, but not in infants with medical NEC (n = 32, p = 0.10). CONCLUSIONS: Of the intestinal-specific proteins evaluated, circulating Gal-4 concentrations were at the assay detection limit in control infants. Gal-4 concentrations were significantly elevated in infants with surgical NEC or SIP, suggesting that Gal-4 may serve as a biomarker for neonatal intestinal injury.
Authors: Sara J Kuik; Willemien S Kalteren; Mirthe J Mebius; Arend F Bos; Jan B F Hulscher; Elisabeth M W Kooi Journal: Pediatr Res Date: 2019-10-24 Impact factor: 3.756
Authors: Darla R Shores; Jennifer Fundora; Mitzi Go; Fauzia Shakeel; Sandra Brooks; Samuel M Alaish; Jun Yang; Chhinder P Sodhi; David J Hackam; Allen Everett Journal: BMC Pediatr Date: 2020-05-26 Impact factor: 2.125