Apoptosis and autoimmunity as proposed pathogenetic links between Helicobacter pylori infection and idiopathic achalasia.
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.
Kountouras
Jannis
J
Department of Gastroenterology, 2nd Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. jannis@med.auth.gr
Zavos
Christos
C
Chatzopoulos
Dimitrios
D
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D004931:Esophageal Achalasia / Q000209:etiology* / Q000276:immunology* / Q000382:microbiology; D019317:Evidence-Based Medicine; D016481:Helicobacter Infections / Q000150:complications* / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D008954:Models, Biological