Buy Article Permissions and Reprints Abstract

Objective Defective Goblet cells have been proposed to be involved in necrotizing enterocolitis (NEC). The aim was to study the expression of the Goblet cell marker REG4 and its potential involvement in NEC in preterm infants with and without NEC.

Study Design Seventy histologically intact intestinal biopsies were studied: 43 were collected during surgery due to NEC (NEC group: 26.5 ± 3.0 weeks' gestational age [wGA]), and 27 from individuals who underwent surgery due to other conditions (Control group; 36.1 ± 4.5 wGA). The tissue samples were immunohistochemically stained for REG4. REG4 expression was quantified with a semiautomated digital image analysis and with clinical data compared between the groups.

Results REG4 expression was lower in the NEC group than in the Control group (p = 0.035). Low REG4 expression correlated to the risk of NEC (p = 0.023). In a multivariable logistic regression analysis including GA and REG4 expression for NEC risk, only GA (p < 0.001) and not REG4 expression (p = 0.206) was associated with NEC risk.

Conclusion This study concludes that Goblet cell dysfunction may be involved in NEC development, as low expression of the Goblet cell marker REG4 was related to an increased NEC risk in preterm infants. Maturity could however not be excluded as a potential confounder for REG4 expression.

Key Points

REG4 is a specific Goblet cell marker not yet studied in NEC.

REG4 was quantified in intestinal biopsies from infants with and without NEC.

REG4 expression was lower in infants with NEC, and expression seems to be maturity dependent.

Keywords necrotizing enterocolitis - Goblet cell - REG4 Authors' Contributions

A.H. performed the collection of data and the statistical analysis and wrote and edited the manuscript. L.M. set up the study, performed data collection, data analysis, and partook in writing and revising the manuscript. H.E.L. partook in data analysis and in writing and revising the manuscript. R.S. performed data analysis, statistical analysis, as well as writing and revising of the manuscript. H.M.F. participated in data collection and data analysis, as well as writing and revising the manuscript.

Ethical Approval

Written informed consent was required from the parents of the infants and from the adult participants included in this study. The Regional Ethical Review Board in Sweden approved this study (approval no.: 2019-00,437).

Publication History

Received: 18 March 2024

Accepted: 27 May 2024

Article published online:
15 July 2024

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