Necrotizing enterocolitis (NEC) is a major cause of mortality in preterm infants. Its pathophysiology remains poorly understood but intestinal epithelial barrier dysfunction contributes to the disease. We characterized junctional proteins in intestinal specimens from preterm infants. Samples from 27 patients with NEC and 20 patients with focal intestinal perforation (FIP) from the center of the specimens (affected) or the macroscopically healthy resection margins whenever available (non-affected) were collected. NEC patients displayed higher mortality and more commonly occurrence of impaired glucose homeostasis, patent ductus arteriosus, anemia and antibiotic treatment compared to FIP patients. Discrimination between NEC and FIP was not possible in affected areas based on H.E. staining using a newly developed scoring system. Immunofluorescence revealed reduced Claudin-3 in affected NEC samples and decreased Claudin-4 in affected FIP and all NEC samples. E-cadherin and Desmoglein-2 were reduced in a subgroup of the affected NEC samples. Plakophilin-2 was decreased in intestine affected by FIP and unaffected intestine in patients with NEC. In affected areas of NEC, Plakophilin-2 was completely lost. Plakoglobin reduction in affected NEC samples correlated with poor survival. This study provides novel insights into changes of junctional proteins in NEC, suggesting Claudin-3 and Plakophilin-2 as diagnostic markers to differentiate FIP from NEC and reduced Plakoglobin as a prognostic marker.
Keywords: Gut barrier; Intestinal epithelial barrier; Junctional proteins; Necrotizing enterocolitis; Preterm infants.
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