Background and aims: Reduced ileal Paneth cell alpha-defensin expression has been reported to be associated with Crohn's disease (CD), especially in patients carrying NOD2 mutations. The aim of this study was to independently assess whether NOD2, alpha-defensins and CD are linked.
Methods: Using quantitative RT-PCR, we measured the mRNA expression levels of key Paneth cell antimicrobial peptides (DEFA5, DEFA6, LYZ, PLA2G2A), inflammatory cytokines (IL6, IL8), and a marker of epithelial cell content, villin (VIL1) in 106 samples from both affected ileum (inflamed CD cases, n=44) and unaffected ileum (non-inflamed; CD cases, n=51 and controls, n=11). Anti-human defensin 5 (HD-5) and haematoxylin/eosin immunohistochemical staining was performed on parallel sections from NOD2 wild-type and NOD2 mutant ileal CD tissue.
Results: In CD patients, DEFA5 and DEFA6 mRNA expression levels were 1.9- and 2.2-fold lower, respectively, in histologically confirmed inflamed ileal mucosa after adjustment for confounders (DEFA5, P < 0.001; DEFA6, P = 0.001). In contrast to previous studies, we found no significant association between alpha-defensin expression and NOD2 genotype. HD-5 protein data supports these RNA findings. The reduction in HD-5 protein expression appears due to surface epithelial cell loss and reduced Paneth cell numbers as a consequence of tissue damage.
Conclusions: Reduction in alpha-defensin expression is independent of NOD2 status and is due to loss of surface epithelium as a consequence of inflammatory changes rather than being the inciting event prior to inflammation in ileal CD.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.