Sammy M Tabbah1, Catalin S Buhimschi1, Katherine Rodewald-Millen1, Christopher R Pierson2,3,4, Vineet Bhandari5, Philip Samuels1, Irina A Buhimschi6,7. 1. Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio. 2. Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio. 3. Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio. 4. Department of Biomedical Education and Anatomy, The Ohio State University College of Medicine, Columbus, Ohio. 5. Department of Pediatrics, Drexel University College of Medicine, Philadelphia, Pennsylvania. 6. Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio. 7. Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio.
Abstract
OBJECTIVE: Hepcidin, a mediator of innate immunity, binds the iron exporter ferroportin, leading to functional hypoferremia through intracellular iron sequestration. We explored hepcidin-ferroportin interactions in neonates clinically diagnosed with early-onset neonatal sepsis (EONS). STUDY DESIGN: Hepcidin and interleukin (IL)-6 were quantified by enzyme-linked immunosorbent assay (ELISA) in 92 paired cord blood-maternal blood samples in the following groups: "Yes" EONS (n = 41, gestational age [GA] 29 ± 1 weeks) and "No" EONS (n = 51, GA 26 ± 1 weeks). Placental hepcidin and ferroportin expression were evaluated by immunohistochemistry and real-time-polymerase chain reaction (RT-PCR). Liver hepcidin and ferroportin expression patterns were ascertained in autopsy specimens of neonates (n = 8) who died secondary to culture-proven sepsis. RESULTS: Cord blood hepcidin was significantly elevated (GA corrected, p = 0.018) and was positively correlated with IL-6 (r = 0.379, p = 0.001) in EONS. Hepcidin localized at syncytiotrophoblast and fetal vascular endothelium. Placental ferroportin, but not hepcidin mRNA correlated with cord blood hepcidin levels (r = 0.46, p = 0.039) and funisitis severity (r = 0.50, p = 0.018). Newborns who died from sepsis (n = 4) had higher hepatic hepcidin and iron sequestration, but lower ferroportin staining than those who died of nonsepsis causes (n = 4). CONCLUSION: Premature fetuses with EONS have elevated circulating hepcidin, likely related to lower placenta and liver ferroportin expression. Fetal hepcidin-ferroportin interaction appears to play a role in EONS pathophysiology independent of maternal response to intrauterine inflammation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
OBJECTIVE:Hepcidin, a mediator of innate immunity, binds the iron exporter ferroportin, leading to functional hypoferremia through intracellular iron sequestration. We explored hepcidin-ferroportin interactions in neonates clinically diagnosed with early-onset neonatal sepsis (EONS). STUDY DESIGN:Hepcidin and interleukin (IL)-6 were quantified by enzyme-linked immunosorbent assay (ELISA) in 92 paired cord blood-maternal blood samples in the following groups: "Yes" EONS (n = 41, gestational age [GA] 29 ± 1 weeks) and "No" EONS (n = 51, GA 26 ± 1 weeks). Placental hepcidin and ferroportin expression were evaluated by immunohistochemistry and real-time-polymerase chain reaction (RT-PCR). Liver hepcidin and ferroportin expression patterns were ascertained in autopsy specimens of neonates (n = 8) who died secondary to culture-proven sepsis. RESULTS: Cord blood hepcidin was significantly elevated (GA corrected, p = 0.018) and was positively correlated with IL-6 (r = 0.379, p = 0.001) in EONS. Hepcidin localized at syncytiotrophoblast and fetal vascular endothelium. Placental ferroportin, but not hepcidin mRNA correlated with cord blood hepcidin levels (r = 0.46, p = 0.039) and funisitis severity (r = 0.50, p = 0.018). Newborns who died from sepsis (n = 4) had higher hepatic hepcidin and iron sequestration, but lower ferroportin staining than those who died of nonsepsis causes (n = 4). CONCLUSION: Premature fetuses with EONS have elevated circulating hepcidin, likely related to lower placenta and liver ferroportin expression. Fetal hepcidin-ferroportin interaction appears to play a role in EONS pathophysiology independent of maternal response to intrauterine inflammation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Authors: Allison L Fisher; Veena Sangkhae; Pietro Presicce; Claire A Chougnet; Alan H Jobe; Suhas G Kallapur; Sammy Tabbah; Catalin S Buhimschi; Irina A Buhimschi; Tomas Ganz; Elizabeta Nemeth Journal: JCI Insight Date: 2020-02-27
Authors: Stephanie Y Tseng; Zhiqian Gao; Theodosia A Kalfa; Nicholas J Ollberding; Sammy Tabbah; Regina Keller; James F Cnota Journal: Pediatr Res Date: 2021-02-02 Impact factor: 3.756