{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:47:58Z","timestamp":1790704078483,"version":"4.1.0"},"reference-count":36,"publisher":"Society for Neuroscience","issue":"49","license":[{"start":{"date-parts":[[2009,6,3]],"date-time":"2009-06-03T00:00:00Z","timestamp":1243987200000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2008,12,3]]},"abstract":"<jats:p>Despite strong circumstantial evidence for the autoimmune hypothesis of narcolepsy, conventional immunological methods have failed to detect an autoantibody. This study investigated the real-time effects of narcoleptic immunoglobulins on a spontaneous colonic migrating motor complex (CMMC) preparation. IgG from patients with narcolepsy with cataplexy or healthy controls was added directly to isolated mouse colons undergoing CMMC activity to test for autoantibodies that disrupt colonic motility. The effect of immunoglobulins prepared for clinical intravenous treatment (IVIg) on autoantibody-mediated colonic disruption was also assessed. Narcoleptic IgGs markedly reduced the frequency of CMMCs or irreversibly abolished them. Abrogation of CMMCs was followed by an increase in the resting tension of the colon preparation and appearance of atropine-sensitive phasic smooth muscle contractions. IVIg partially neutralized the inhibitory effect of narcoleptic IgG on the CMMCs. The dramatic effect of narcoleptic IgG on CMMC generation is consistent with an autoantibody-mediated disruption of enteric neural pathways. The<jats:italic>ex vivo<\/jats:italic>whole-organ approach allows real-time examination of the physiological effects of the narcoleptic autoantibody and offers a new avenue for exploring the autoimmune basis of narcolepsy. The neutralizing effect of IVIg on the autoantibody provides a rationale for the reported clinical improvement in cataplexy when IVIg are given at disease onset.<\/jats:p>","DOI":"10.1523\/jneurosci.4489-08.2008","type":"journal-article","created":{"date-parts":[[2008,12,3]],"date-time":"2008-12-03T20:16:24Z","timestamp":1228335384000},"page":"13303-13309","source":"Crossref","is-referenced-by-count":23,"title":["An Autoantibody in Narcolepsy Disrupts Colonic Migrating Motor Complexes"],"prefix":"10.1523","volume":"28","author":[{"given":"Michael W.","family":"Jackson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne H.","family":"Reed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J. F.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom P.","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2008,12,3]]},"reference":[{"key":"2023041303352306000_28.49.13303.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2007.11.006"},{"key":"2023041303352306000_28.49.13303.2","doi-asserted-by":"publisher","DOI":"10.1080\/02646830500381492"},{"key":"2023041303352306000_28.49.13303.3","first-page":"1191","article-title":"HLA DQB1*0602 positive narcoleptic subjects with cataplexy have CSF lgG reactive to rat hypothalamic protein extract","volume":"28","author":"Black","year":"2005","journal-title":"Sleep"},{"key":"2023041303352306000_28.49.13303.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2005.04.026"},{"key":"2023041303352306000_28.49.13303.5","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1093\/sleep\/28.4.427","article-title":"Analysis of hypocretin (orexin) antibodies in patients with narcolepsy","volume":"28","author":"Black","year":"2005","journal-title":"Sleep"},{"key":"2023041303352306000_28.49.13303.6","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000175219.01544.c8"},{"key":"2023041303352306000_28.49.13303.7","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10205"},{"key":"2023041303352306000_28.49.13303.8","doi-asserted-by":"publisher","DOI":"10.1002\/art.11343"},{"key":"2023041303352306000_28.49.13303.9","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000168173.71940.ab"},{"key":"2023041303352306000_28.49.13303.10","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20339"},{"key":"2023041303352306000_28.49.13303.11","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2982.1997.d01-25.x"},{"key":"2023041303352306000_28.49.13303.12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2008.01836.x"},{"key":"2023041303352306000_28.49.13303.13","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.12.015"},{"key":"2023041303352306000_28.49.13303.14","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.3.321"},{"key":"2023041303352306000_28.49.13303.15","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-1319"},{"key":"2023041303352306000_28.49.13303.16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra993360"},{"key":"2023041303352306000_28.49.13303.17","doi-asserted-by":"publisher","DOI":"10.1086\/318799"},{"key":"2023041303352306000_28.49.13303.18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00219.2001"},{"key":"2023041303352306000_28.49.13303.19","doi-asserted-by":"publisher","DOI":"10.1097\/00004691-200103000-00002"},{"key":"2023041303352306000_28.49.13303.20","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1212\/01.WNL.0000101718.92619.67","article-title":"Hypocretin-1 CSF levels in anti-Ma2 associated encephalitis","volume":"62","author":"Overeem","year":"2004","journal-title":"Neurology"},{"key":"2023041303352306000_28.49.13303.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2006.02.010"},{"key":"2023041303352306000_28.49.13303.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2007.07.010"},{"key":"2023041303352306000_28.49.13303.23","doi-asserted-by":"publisher","DOI":"10.1038\/79690"},{"key":"2023041303352306000_28.49.13303.24","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfl523"},{"key":"2023041303352306000_28.49.13303.25","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1212\/WNL.48.6.1550","article-title":"HLA DR15 (DR2) and DQB1*0602 typing studies in 188 narcoleptic patients with cataplexy","volume":"48","author":"Rogers","year":"1997","journal-title":"Neurology"},{"key":"2023041303352306000_28.49.13303.26","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10444"},{"key":"2023041303352306000_28.49.13303.27","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1093\/sleep\/29.5.601","article-title":"The frustrating and mostly fruitless search for an autoimmune cause of narcolepsy","volume":"29","author":"Scammell","year":"2006","journal-title":"Sleep"},{"key":"2023041303352306000_28.49.13303.28","doi-asserted-by":"publisher","DOI":"10.1097\/01.scs.0000180285.51365.55"},{"key":"2023041303352306000_28.49.13303.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17553-3"},{"key":"2023041303352306000_28.49.13303.30","first-page":"A168","article-title":"Activity of passively transferred narcolepsy IgG may be influenced by genetic background and immune cofactors","volume":"5","author":"Smith","year":"2007","journal-title":"Sleep Biol Rhythms"},{"key":"2023041303352306000_28.49.13303.31","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1838(98)00063-0"},{"key":"2023041303352306000_28.49.13303.32","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(69)90285-9"},{"key":"2023041303352306000_28.49.13303.33","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1093\/sleep\/29.5.633","article-title":"Detection of autoantibodies against hypocretin, hcrtrl, and hcrtr2 in narcolepsy: anti-Hcrt system antibody in narcolepsy","volume":"29","author":"Tanaka","year":"2006","journal-title":"Sleep"},{"key":"2023041303352306000_28.49.13303.34","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00058-1"},{"key":"2023041303352306000_28.49.13303.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2008.03.004"},{"key":"2023041303352306000_28.49.13303.36","doi-asserted-by":"crossref","unstructured":"Waterman SA Jackson MW Gordon TP (2006) in Functional effects of autoantibodies: the autoimmune diseases, eds Rose NR Mackay IR (Elsevier, Sydney), Ed 4, pp 217\u2013236.","DOI":"10.1016\/B978-012595961-2\/50020-2"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.4489-08.2008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T18:58:05Z","timestamp":1681412285000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.4489-08.2008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,12,3]]},"references-count":36,"journal-issue":{"issue":"49","published-online":{"date-parts":[[2008,12,3]]},"published-print":{"date-parts":[[2008,12,3]]}},"alternative-id":["10.1523\/JNEUROSCI.4489-08.2008"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.4489-08.2008","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,12,3]]}}}