Akihiro Mukaino1, Hitomi Minami2, Hajime Isomoto2, Hitomi Hamamoto3, Eikichi Ihara4, Yasuhiro Maeda5,6,7, Osamu Higuchi6, Tohru Okanishi8, Yohei Kokudo9, Kazushi Deguchi9, Fumisato Sasaki3, Toshihito Ueki10, Ken-Ya Murata11, Takeshi Yoshida12, Mistuyo Kinjo12, Yoshihiro Ogawa4, Akio Ido3, Hidenori Matsuo7, Kazuhiko Nakao2, Shunya Nakane13,14,15. 1. First Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. 2. Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. 3. Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. 4. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 5. Department of Neuroimmunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. 6. Department of Clinical Research, Nagasaki Kawatana Medical Center, 2005-1 Shimogumigo, Kawatanacho, Higashisonogigun, Nagasaki, 859-3615, Japan. 7. Department of Neurology, Nagasaki Kawatana Medical Center, Nagasaki, Japan. 8. Department of Child Neurology, Seirei Hamamatsu General Hospital, Shizuoka, Japan. 9. Department of Neurology, Kagawa University Hospital, Kagawa, Japan. 10. Department of Gastroenterology and Hepatology, Nagasaki Kawatana Medical Center, Nagasaki, Japan. 11. Department of Neurology, Wakayama Medical University, Wakayama, Japan. 12. Department of Medicine and Rheumatology, Okinawa Chubu Hospital, Uruma, Okinawa, Japan. 13. Department of Neuroimmunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. nakaneshunya@gmail.com. 14. Department of Clinical Research, Nagasaki Kawatana Medical Center, 2005-1 Shimogumigo, Kawatanacho, Higashisonogigun, Nagasaki, 859-3615, Japan. nakaneshunya@gmail.com. 15. Department of Neurology, Nagasaki Kawatana Medical Center, Nagasaki, Japan. nakaneshunya@gmail.com.
Abstract
BACKGROUND: The existence of several autoantibodies suggests an autoimmune basis for gastrointestinal (GI) dysmotility. Whether GI motility disorders are features of autoimmune autonomic ganglionopathy (AAG) or are related to circulating anti-ganglionic acetylcholine receptor (gAChR) antibodies (Abs) is not known. The aim of this study was to determine the associations between autonomic dysfunction, anti-gAChR Abs, and clinical features in patients with GI motility disorders including achalasia and chronic intestinal pseudo-obstruction (CIPO). METHODS: First study: retrospective cohort study and laboratory investigation. Samples from 123 patients with seropositive AAG were obtained between 2012 and 2017. Second study: prospective study. Samples from 28 patients with achalasia and 14 patients with CIPO were obtained between 2014 and 2016, and 2013 and 2017, respectively. In the first study, we analyzed clinical profiles of seropositive AAG patients. In the second study, we compared clinical profiles, autonomic symptoms, and results of antibody screening between seropositive, seronegative achalasia, and CIPO groups. RESULTS: In the first study, we identified 10 patients (8.1%) who presented with achalasia, or gastroparesis, or paralytic ileus. In the second study, we detected anti-gAChR Abs in 21.4% of the achalasia patients, and in 50.0% of the CIPO patients. Although patients with achalasia and CIPO demonstrated widespread autonomic dysfunction, bladder dysfunction was observed in the seropositive patients with CIPO as a prominent clinical characteristic of dysautonomia. CONCLUSIONS: These results demonstrate a significant prevalence of anti-gAChR antibodies in patients with achalasia and CIPO. Anti-gAChR Abs might mediate autonomic dysfunction, contributing to autoimmune mechanisms underlying these GI motility disorders.
BACKGROUND: The existence of several autoantibodies suggests an autoimmune basis for gastrointestinal (GI) dysmotility. Whether GI motility disorders are features of autoimmune autonomic ganglionopathy (AAG) or are related to circulating anti-ganglionic acetylcholine receptor (gAChR) antibodies (Abs) is not known. The aim of this study was to determine the associations between autonomic dysfunction, anti-gAChR Abs, and clinical features in patients with GI motility disorders including achalasia and chronic intestinal pseudo-obstruction (CIPO). METHODS: First study: retrospective cohort study and laboratory investigation. Samples from 123 patients with seropositive AAG were obtained between 2012 and 2017. Second study: prospective study. Samples from 28 patients with achalasia and 14 patients with CIPO were obtained between 2014 and 2016, and 2013 and 2017, respectively. In the first study, we analyzed clinical profiles of seropositive AAG patients. In the second study, we compared clinical profiles, autonomic symptoms, and results of antibody screening between seropositive, seronegative achalasia, and CIPO groups. RESULTS: In the first study, we identified 10 patients (8.1%) who presented with achalasia, or gastroparesis, or paralytic ileus. In the second study, we detected anti-gAChR Abs in 21.4% of the achalasiapatients, and in 50.0% of the CIPOpatients. Although patients with achalasia and CIPO demonstrated widespread autonomic dysfunction, bladder dysfunction was observed in the seropositive patients with CIPO as a prominent clinical characteristic of dysautonomia. CONCLUSIONS: These results demonstrate a significant prevalence of anti-gAChR antibodies in patients with achalasia and CIPO. Anti-gAChR Abs might mediate autonomic dysfunction, contributing to autoimmune mechanisms underlying these GI motility disorders.
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