The etiology of achalasia: An immune‐dominant disease

There is accumulating evidence suggesting that an autoimmune component is involved in esophageal achalasia. An increase in immune cells, cytokines, chemokines, and autoimmune antibodies in serum and infiltration of immune cells in tissues support the view that immune‐mediated inflammation is a crucial pathogenesis of inhibitory neuron degeneration in the lower esophageal sphincter. Infection of viruses such as the herpes virus family has been suspected of provoking the autoimmune reaction. Meanwhile, previous reports on immunogenetics have proposed that specific risk alleles on the human leukocyte antigen complex define the susceptible population to achalasia. In this study we reviewed current knowledge regarding the immune‐related factors of achalasia, including immunology, viral infection and immunogenetic variations. Achalasia is an immune‐dominant disease. Susceptible groups with specific immune‐related alleles may infect with viruses, thus triggers an autoimmune response. The autoimmune reaction, including innate immune cells, adaptive immune cells, cytokines, complements and autoantibodies, attacks inhibitory neurons in the lower esophageal sphincter (LES) and causes the persistent contraction of the esophagus. Abbreviations: CMV, cytomegalovirus; HSV, herpes simplex virus; IL, interleukin; Th, T helper; TNF, tumor necrosis factor; VZV, varicella‐zoster virus