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Previous studies supported the hypothesis that autoimmune\u2010mediated inflammatory responses produce inhibitory neuronal degeneration. This study was designed to explore the role of mast cells in achalasia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected information from 116 patients with achalasia who underwent peroral endoscopic myotomy between December 2016 and May 2017. Lower esophageal sphincter (LES) muscle biopsy was performed in all patients with achalasia, as well as 20 control subjects. The number of mast cells, interstitial cells of Cajal (ICCs), nNOS\u2010positive cells, and S\u2010100\u2010positive cells in the LES were evaluated by immunohistochemistry. Pathological and clinical data were compared between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Compared with controls, the LES of patients with achalasia had significantly fewer ICCs, nNOS\u2010positive cells, and S\u2010100\u2010positive cells and a higher number of mast cells (all <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Furthermore, the increased mast cell infiltration was significantly associated with decreased ICCs, nNOS\u2010positive cells, and S\u2010100\u2010positive cells in patients with achalasia (all <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Clinically, the number of strongly positive mast cells was highest in patients with type I achalasia and lowest in those with type III achalasia (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). In addition, patients with a history of autoimmune disease or viral infection had greater mast cell infiltration in the LES muscle (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.040).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>In patients with achalasia, mast cell infiltration in the LES muscle is increased, in association with loss of ICCs and neuronal degeneration. Mast cells may thereby play a crucial role in the development of achalasia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13565","type":"journal-article","created":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T00:50:08Z","timestamp":1552524608000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Mast cell infiltration associated with loss of interstitial cells of Cajal and neuronal degeneration in achalasia"],"prefix":"10.1111","volume":"31","author":[{"given":"Zu\u2010Qiang","family":"Liu","sequence":"first","affiliation":[{"name":"Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Feng","family":"Chen","sequence":"additional","affiliation":[{"name":"Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital Fudan University Shanghai 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