Kountouras Jannis, Zavos Christos, Chatzopoulos Dimitrios
Department of Gastroenterology, 2nd Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Med Hypotheses. 2004;63(4):624-9. doi: 10.1016/j.mehy.2004.04.003.
Achalasia is a disorder of the oesophagus characterised by increased lower oesophageal sphincter (LOS) tone, lack of LOS relaxation with swallowing and aperistalsis of the body of the oesophagus. The aetiology and pathogenesis of idiopathic achalasia are still unclear, although a viral cause, genetic influences (associations with HLA loci) and autoimmune processes have been postulated. Degeneration and significant loss of nerve fibres, associated with an inflammatory infiltrate of the myenteric plexus in idiopathic achalasia, provide evidence of an immune mediated destruction of the myenteric plexus, possibly through apoptotic process. This concept is reinforced by the concomitant appearance of achalasia and Guillain-Barré syndrome (GBS) and/or Parkinson's disease, where inappropriate initiation of apoptosis has been proposed to underlie the neuronal attrition. In the same respect, Helicobacter pylori (H. pylori) infection has been associated with gastric autoimmunity, and patients infected with H. pylori have been shown to possess autoantibodies that cross-react with antigens expressed on the gastric mucosa. Furthermore, H. pylori is thought to be associated with the development of autoimmune sequelae observed in peripheral neuropathies and GBS, where autoantibodies to specific neural targets have been found to impair native neural function by inducing nerve tissue damage, possibly by apoptosis. Taken together, we assume that H. pylori infection might be a pathogenetic factor of achalasia through induction of autoimmunity and apoptosis. Whether eradication of H. pylori infection may indirectly offer benefit to the pathophysiology of idiopathic achalasia by ameliorating the apoptotic loss of ganglion cells and their axons in the oesophageal wall remains to be elucidated.
贲门失弛缓症是一种食管疾病，其特征为食管下括约肌（LOS）张力增加、吞咽时LOS不松弛以及食管体部蠕动消失。尽管已推测存在病毒病因、遗传影响（与HLA基因座相关）和自身免疫过程，但特发性贲门失弛缓症的病因和发病机制仍不清楚。在特发性贲门失弛缓症中，神经纤维变性和显著丧失，伴有肌间神经丛的炎性浸润，这为肌间神经丛的免疫介导破坏提供了证据，可能是通过凋亡过程。贲门失弛缓症与吉兰 - 巴雷综合征（GBS）和/或帕金森病同时出现，进一步强化了这一概念，在这些疾病中，细胞凋亡的不适当启动被认为是神经元损耗的基础。同样，幽门螺杆菌（H. pylori）感染与胃部自身免疫有关，感染H. pylori的患者已被证明拥有与胃黏膜上表达的抗原发生交叉反应的自身抗体。此外，H. pylori被认为与在周围神经病变和GBS中观察到的自身免疫后遗症的发展有关，在这些疾病中，针对特定神经靶点的自身抗体已被发现通过诱导神经组织损伤（可能通过凋亡）来损害天然神经功能。综上所述，我们假设H. pylori感染可能是通过诱导自身免疫和凋亡而成为贲门失弛缓症的致病因素。根除H. pylori感染是否可通过改善食管壁神经节细胞及其轴突的凋亡性丧失而间接对特发性贲门失弛缓症的病理生理学产生益处，仍有待阐明。
