Anti-neuronal autoantibodies can lead to subacute gastrointestinal dysmotility, presenting with various symptoms typical of intestinal pseudoobstruction, achalasia, gastroparesis, or slow intestinal transit, among others. Such autoantibodies may be produced in response to a remote tumor and accelerate the diagnosis of malignancy, but in other cases they appear without an identifiable underlying cause. One example is the type I anti-neuronal nuclear antibody (ANNA-1 otherwise known as anti-Hu), which is usually linked to small cell-lung carcinoma. Anti-Hu can directly activate enteric neurons and visceral sensory nerve fibers and has a cytotoxic effect. Various other anti-neuronal antibodies have been described, targeting different ion channels or receptors on nerve cells of the central or the enteric nervous system. Autoimmune processes targeting enteric neurons may also play a role in more common disorders such as esophageal achalasia, celiac disease, or multiple sclerosis. Furthermore, anti-enteric neuronal antibodies have been found more abundant in the common functional gastrointestinal disorder, irritable bowel syndrome (IBS), than in controls. The pathogenesis of IBS is very complex, involving the release of various mediators from immune cells in the gut wall. Products of mast cells, such as histamine and tryptase, excite visceral afferents and enteric neurons, which may contribute to symptoms like abdominal pain and disturbed motility. Elevated serine- and cysteine-protease activity in stool of IBS-D and IBS-C patients, respectively, can be a factor leading to leaky gut and visceral hypersensitivity. More knowledge on these mediators in IBS may facilitate the development of novel diagnostic methods or therapies.
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