ABSTRACT Background Recent clinical trials have shown a promising role for appendectomy in the treatment of ulcerative colitis (UC). However, as with medical treatment, only a subset of patients responds to the intervention. A lack of predictive markers and knowledge on the mechanism of action of appendectomy in UC currently precludes affective patient selection. Methods We performed transcriptional profiling and cellular deconvolution on the appendices obtained in the course of the recent clinical studies. Data were verified by immunohistochemistry. Results When comparing responders to nonresponders, initially very few differentially expressed genes were observed (7 up and 6 down). However, unsupervised clustering revealed a dichotomy in the samples which was the results of underlying phenotypic differences. One group mainly displayed stromal characteristic, whereas the other expressed intestinal epithelial genes. These data were verified by deconvolution and immunohistochemistry. Importantly, within each subtype, distinct gene expression patterns were correlated with response to appendectomy. Interestingly, although in both subtypes activity was associated with immune activation, in the stromal group, this was a predominantly innate response, whereas in the epithelial group, the response was more adaptive in nature. Conclusions In patients with UC two distinct phenotypic subtypes of appendix were observed. Although both groups had the potential to respond to appendectomy, response was associated with different immune activity patterns in each group. These data strongly suggest that there may be two individual mechanism of action for appendectomy in UC, which will be important to account for in future studies.
Becker et al. (Sun,) studied this question.
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