Background: The enteric nervous system can amplify or modulate intestinal inflammation through secretion of neuropeptides, and enteric glial cells has been implicated in the pathophysiology of Crohn's disease. The goal of the study was to search for an association between the density of neurons, neuropeptides, as well as enteric glial cells and postoperative disease recurrence in patients with Crohn's disease.
Methods: Ileocolonic samples obtained from 30 patients with Crohn's disease receiving azathioprine for prophylaxis in our previously reported clinical trial. The ileal proximal uninflamed section was studied using immunohistochemistry with antibodies directed against vasoactive intestinal polypeptide (VIP), substance P (SP), neuron-specific enolase (NES), and the glial marker protein S100. The density in the submucosa was defined as the ratio between the cumulated surface area and the total microscopic fields, and was expressed as mean percent. The relationship of the density of VIP, SP, NES, and S100 and postoperative disease recurrence was assessed.
Results: There were no significant differences between patients with and without postoperative endoscopic recurrence for the density of NSE-positive (3.38±1.22 versus 3.75±1.45, p=0.481), VIP-positive (1.51±0.62 versus 1.24±0.82, p=0.320) or SP-positive neurones (1.63±0.94 versus 1.21±0.32, p=0.201) in the proximal margin. Interestingly, a significant difference was found concerning the number of EGC (S100-positive) (1.39±0.41 versus 0.55±0.29, p<0.001) in endoscopic recurrence than in cases without endoscopic recurrence. No differences were found between patients presence and absence of postoperative clinical recurrence in terms of NSE-positive (3.75±0.61 versus 3.40±1.45, p=0.528), VIP-positive (1.26±0.36 versus 1.49±0.76, p=0.418) or SP-positive neurones (1.49±0.97 versus 1.51±0.79, p=0.965). However, the density of S100-positive enteric glial cells (1.70±0.38 versus 0.93±0.43, p<0.001) was significantly increased in patients with clinical recurrence than in subjects without clinical recurrence (Figure 1).
Conclusions: Increased S100-positive enteric glial cells is associated with high risk of both endoscopic and clinical recurrence after surgery. These findings have implications in individualized postoperative prophylaxis for Crohn's disease.