Mayo Clinic has a distinguished history of investigating neural autoimmune disorders. An important aspect of this work concerns the occurrence of autonomic disease in an immune setting and the discovery that immunotherapy can be beneficial for patients with autonomic disease.
Although autonomic disease is typically associated with syncope, neuropathy and sweating problems, chronic gastrointestinal (GI) dysmotility also may be a component. Autoimmune GI dysmotility (AGID) is a newly described clinical entity that is a limited manifestation of autoimmune dysautonomia, and can occur as an idiopathic phenomenon. Signs and symptoms include early satiety, nausea, vomiting, bloating, diarrhea, constipation and involuntary weight loss. The onset may be subacute, and neurological manifestations may or may not be an accompaniment.
In the September 2014 issue of Neurogastroenterology & Motility, Mayo Clinic researchers report the first objective evidence that immunotherapy may reverse autoimmune GI dysmotility. The study illustrates the importance of considering an autoimmune basis for acquired idiopathic GI motility disorders.
"The concept that you can have predominantly GI dysmotility — without necessarily having a lot of symptoms in other areas — and the conclusion that it is due to an immune mechanism affecting the nervous system of the gut is rather novel," says Sean J. Pittock, M.D., a consultant in the Department of Neurology at Mayo Clinic in Rochester, Minnesota, and founder of the autoimmune neurology clinic there. "But if the immune system can cause inflammation of the optic nerve, spinal cord or cerebral cortex, then why can't it cause a problem with the gut? After all, the gut contains 100 million neurons — more than the spinal cord or the peripheral nervous system."
AGID appears to be relatively uncommon; most GI symptoms are caused by other diseases or have a functional basis — for example, irritable bowel syndrome. The term "dysmotility" refers to abnormal movement of food, nutrients and waste through the digestive tract. With AGID, the presumption is that the nerves controlling the GI tract are being targeted by immune cells, resulting in altered neural function and thus, altered GI transit.
AGID can be disabling. "Patients who have these problems are miserable. They have no appetite. They have terrible abdominal pains and constipation. Often these patients undergo lots of diagnostic testing and multiple consultations," says Lawrence A. Szarka, M.D., a consultant in the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester, Minnesota.
The Mayo Clinic research was a retrospective case study of 23 patients seen at Mayo Clinic for suspected AGID, in whom an immunotherapy trial was undertaken. Seventeen of the patients improved after the six- to 12-week immunotherapy trial. Autoimmune serological evaluation revealed a neural-specific antibody in 12 of the 17 responders (71 percent). Symptomatic improvements were generally accompanied by objective evidence of improved GI motility and autonomic function on repeated scintigraphic, manometric and autonomic function tests.
"The observation that the immune system may be attacking parts of the nervous system and causing disorders that we might have explained away as a functional problem opens up possibilities for new, directed therapies to help the patient's GI symptoms," says Joseph A. Murray, M.D., a consultant in the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester, Minnesota.
"Treatment options for gastroparesis — a condition where the stomach does not empty food — are extremely limited, and the ones that exist merely facilitate gastric emptying or treat the symptoms. The idea that there may be a treatment that targets the underlying cause of gastroparesis is exciting," says Yuri A. Saito Loftus, M.D., a consultant in the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester, Minnesota.
Blood test (anti-CdtB and anti-vinculin) for IBS now available at Quest