332 - Paneth Cell Proteins DEFA6 and GUCA2A as Tissue Markers in Necrotizing Enterocolitis

Background: Previous studies suggest that Paneth cells are involved in NEC development. Defensin alpha 6 (DEFA6) and Guanylate cyclase activator 2A (GUCA2A) are selective protein markers of Paneth cells. A few studies have investigated alpha-defensin expression (DEFA6 and DEFA5) in NEC with inconsistent results, showing that defensin levels may be increased or diminished in NEC. GUCA2A has to our knowledge not previously been studied in NEC.

Objective:

Objective: The objective was to explore DEFA6 and GUCA2A expression in intestinal tissue samples from newborn infants with and without NEC.

 

Design/Methods:

METHODS: Tissue samples from histologically intact intestine were analyzed from 70 infants: 43 underwent bowel resection due to NEC and 27 controls were operated due to conditions such as intestinal atresia, dysmotility, aganglionosis, pseudo-obstruction or volvulus. Only samples of histologically intact intestine from the ends of the resected intestine were included in this study. Each tissue sample was immunohistochemically stained for DEFA6 and GUCA2A. Semi-automated digital image analysis was performed to determine protein expression. Clinical data and protein expressions were compared between the groups.

 

Results:

Results: DEFA6-expression was lower in the NEC-group (p=0.006). Low DEFA6 correlated with risk for developing NEC in a logistic regression analysis, independently of gestational age and birth weight (OR 0.843 [CI 0.732-0.971]; p=0.018). GUCA2A-expression did not differ between the two groups.

Conclusion(s):

Conclusions: This study defines the expression of DEFA6 and GUCA2A in viable tissue before it is histologically affected by NEC, Lower expression of DEFA6 together with intact GUCA2A-expression indicates that NEC-patients have well defined Paneth cells but diminished defensin activity.  Our results suggest that DEFA6 could be used as a biomarker for NEC.


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