Akihiro Mukaino1, Shunya Nakane2,3, Osamu Higuchi2, Hideki Nakamura4, Tomo Miyagi5, Kanako Shiroma5, Takashi Tokashiki5, Yasuhiro Fuseya6, Kazuhide Ochi7, Masataka Umeda4, Tetsuya Nakazato8, Shinji Akioka9, Hiroyuki Maruoka10, Masatoshi Hayashi11, Shu-Ichi Igarashi12, Katsunori Yokoi13, Yasuhiro Maeda3, Waka Sakai3, Hidenori Matsuo3, Atsushi Kawakami4. 1. a Department of Clinical Neuroscience and Neurology , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan . 2. b Department of Clinical Research and. 3. c Department of Neurology , Nagasaki Kawatana Medical Center , Nagasaki , Japan . 4. d Department of Immunology and Rheumatology , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan . 5. e Department of Cardiovascular Medicine, Nephrology and Neurology , University of the Ryukyu School of Medicine , Okinawa , Japan . 6. f Department of Neurology , Kitano Hospital Medical Research Institute , Osaka , Japan . 7. g Department of Neurology , Hiroshima University Hospital , Hiroshima , Japan . 8. h Department of Neurology , Sapporo Yamanoue Hospital , Sapporo , Japan . 9. i Department of Pediatrics, Graduate School of Medical Science , Kyoto Prefectural University of Medicine , Kyoto , Japan . 10. j Department of Neurology and Neurological Science, and Predictive and Preventive Medicine , Tokyo Medical and Dental University , Tokyo , Japan . 11. k Department of Pediatrics , Uwajima City Hospital , Ehime , Japan . 12. l Department of Neurology , Niigata City General Hospital , Niigata , Japan , and. 13. m Department of Neurology , Anjo Kosei Hospital , Aichi , Japan.
Abstract
OBJECTIVE: It is not known whether autonomic neuropathy is a feature of Sjögren's syndrome (SS) or whether it is related to circulating antiganglionic acetylcholine receptor (gAChR) antibodies. The goal of the present study was to investigate the autonomic dysfunction in patients with SS and the associations between autonomic dysfunction, anti-gAChR antibodies, and clinical features of SS. METHODS: (1) The first observational study tested for the presence of gAChR antibodies in the serum samples from 39 patients with SS (absent information regarding autonomic symptoms) and healthy volunteers. (2) In the second study, serological and clinical data from 10 Japanese patients diagnosed with SS were reviewed. These patients showed autonomic dysfunction, and luciferase immunoprecipitation systems (LIPS) test was conducted to detect anti-α3 and anti-β4 gAChR antibodies. (3) In the final analysis, we combined the data of seropositive SS patients with autonomic symptom from the first study with all of the patients from the second study, and analyzed the clinical features. RESULTS: (1) The LIPS assay revealed that anti-gAChRα3 and anti-gAChRβ4 antibodies were detected in the sera from patients with SS (23.1%, 9/39). Five of nine SS patients had autonomic symptoms. (2) Anti-α3 and anti-β4 gAChR antibodies were also detected in 80.0% (8/10) of patients with SS with autonomic symptoms. Six of the ten patients were diagnosed as having SS after neurological symptoms developed. These seropositive patients had predominant and severe autonomic symptoms and were diagnosed with autonomic neuropathy. (3) Thirteen of fifteen SS patients with autonomic symptoms (86.7%) were seropositive for anti-gAChR antibodies, and we confirmed sicca complex, orthostatic hypotension, upper and lower gastrointestinal (GI) symptoms, and bladder dysfunction at high rates. CONCLUSION: The present results suggest the possibility of anti-gAChR antibodies aiding the diagnostics of SS with autonomic dysfunction.
OBJECTIVE: It is not known whether autonomic neuropathy is a feature of Sjögren's syndrome (SS) or whether it is related to circulating antiganglionic acetylcholine receptor (gAChR) antibodies. The goal of the present study was to investigate the autonomic dysfunction in patients with SS and the associations between autonomic dysfunction, anti-gAChR antibodies, and clinical features of SS. METHODS: (1) The first observational study tested for the presence of gAChR antibodies in the serum samples from 39 patients with SS (absent information regarding autonomic symptoms) and healthy volunteers. (2) In the second study, serological and clinical data from 10 Japanese patients diagnosed with SS were reviewed. These patients showed autonomic dysfunction, and luciferase immunoprecipitation systems (LIPS) test was conducted to detect anti-α3 and anti-β4 gAChR antibodies. (3) In the final analysis, we combined the data of seropositive SS patients with autonomic symptom from the first study with all of the patients from the second study, and analyzed the clinical features. RESULTS: (1) The LIPS assay revealed that anti-gAChRα3 and anti-gAChRβ4 antibodies were detected in the sera from patients with SS (23.1%, 9/39). Five of nine SS patients had autonomic symptoms. (2) Anti-α3 and anti-β4 gAChR antibodies were also detected in 80.0% (8/10) of patients with SS with autonomic symptoms. Six of the ten patients were diagnosed as having SS after neurological symptoms developed. These seropositive patients had predominant and severe autonomic symptoms and were diagnosed with autonomic neuropathy. (3) Thirteen of fifteen SS patients with autonomic symptoms (86.7%) were seropositive for anti-gAChR antibodies, and we confirmed sicca complex, orthostatic hypotension, upper and lower gastrointestinal (GI) symptoms, and bladder dysfunction at high rates. CONCLUSION: The present results suggest the possibility of anti-gAChR antibodies aiding the diagnostics of SS with autonomic dysfunction.