We read with interest the recent research article by Lisa Simms and her colleagues (Gut 2008;57:903–10). While we agree with Simms et al that the NOD2 genotype is an important variable in the study of ileal Crohn’s disease (CD), we disagree with her conclusion that α-defensin expression is related to inflammation rather than NOD2 status. This genotype is especially important in the analysis of Paneth cell antimicrobial expression, given the prominent expression of NOD2 in Paneth cells.1 In a previous investigation, we reported a significant association of the NOD2 genotype with HD5 mRNA expression levels (Wehkamp et al,2 fig 1D), but, importantly, the effect was found only with the 1007fs mutation (SNP13). The decrease of HD5 levels with the 1007fs NOD2 genotype was confirmed at the protein level by western blot analysis (Wehkamp et al,2 fig 1E). The significance of the western blot data was emphasised by our observation that the same 1007fs samples had no decrease in levels of either sPLA2, lysozyme or α-1-antiprotease, three other Paneth cell proteins (Wehkamp et al,2 fig 1G). Of special note, we saw no association of either the R702W or G908R genotypes with HD5 mRNA levels (Wehkamp et al,2 fig 1D). In their recent paper, Simms et al did not stratify their genotype data to investigate if there was a difference in HD5 expression levels associated with any particular NOD2 genotype. Since eight patients in their cohort had a 1007fs mutation, we …