{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:03:00Z","timestamp":1788184980683,"version":"build-2803163510"},"reference-count":29,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T00:00:00Z","timestamp":1571270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"nci","award":["K12CA215110"],"award-info":[{"award-number":["K12CA215110"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["j. immunotherapy cancer"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1186\/s40425-019-0748-0","type":"journal-article","created":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T11:32:48Z","timestamp":1571311968000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Seronegative autoimmune autonomic ganglionopathy from dual immune checkpoint inhibition in a patient with metastatic melanoma"],"prefix":"10.1136","volume":"7","author":[{"given":"Catherine A.","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urs M.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo J.","family":"Peixoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2019,10,17]]},"reference":[{"key":"748_CR1","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1056\/NEJMoa1302369","volume":"369","author":"JD Wolchok","year":"2013","unstructured":"Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang XL, Lowy I, Inzunza HD, Feely W, Horak CE, Hong Q, Korman AJ, Wigginton JM, Gupta A, Sznol M. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369:122\u201333. \n                    https:\/\/doi.org\/10.1056\/NEJMoa1302369\n                    \n                  .","journal-title":"N Engl J Med"},{"key":"748_CR2","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1056\/NEJMoa1414428","volume":"372","author":"MA Postow","year":"2015","unstructured":"Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor D, Salama AK, Taylor M, Ott PA, Rollin LM, Horak C, Gagnier P, Wolchok JD, Hodi FS. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372:2006\u201317. \n                    https:\/\/doi.org\/10.1056\/NEJMoa1414428\n                    \n                  .","journal-title":"N Engl J Med"},{"key":"748_CR3","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1056\/NEJMoa1504030","volume":"373","author":"J Larkin","year":"2015","unstructured":"Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23\u201334. \n                    https:\/\/doi.org\/10.1056\/NEJMoa1504030\n                    \n                  .","journal-title":"N Engl J Med"},{"key":"748_CR4","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1016\/s0140-6736(17)31601-x","volume":"390","author":"J Schachter","year":"2017","unstructured":"Schachter J, Ribas A, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank C, Petrella TM, Hamid O, Zhou HH, Ebbinghaus S, Ibrahim N, Robert C. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet. 2017;390:1853\u201362. \n                    https:\/\/doi.org\/10.1016\/s0140-6736(17)31601-x\n                    \n                  .","journal-title":"Lancet"},{"key":"748_CR5","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1056\/NEJMoa1709684","volume":"377","author":"JD Wolchok","year":"2017","unstructured":"Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, Lao CD, Wagstaff J, Schadendorf D, Ferrucci PF, Smylie M, Dummer R, Hill A, Hogg D, Haanen J, Carlino MS, Bechter O, Maio M, Marquez-Rodas I, Guidoboni M, McArthur G, Lebbe C, Ascierto PA, Long GV, Cebon J, Sosman J, Postow MA, Callahan MK, Walker D, Rollin L, Bhore R, Hodi FS, Larkin J. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377:1345\u201356. \n                    https:\/\/doi.org\/10.1056\/NEJMoa1709684\n                    \n                  .","journal-title":"N Engl J Med"},{"key":"748_CR6","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s40425-018-0393-z","volume":"6","author":"CA Garcia","year":"2018","unstructured":"Garcia CA, El-Ali A, Rath TJ, Contis LC, Gorantla V, Drappatz J, Davar D. Neurologic immune-related adverse events associated with adjuvant ipilimumab: report of two cases. J Immunother Cancer. 2018;6:83. \n                    https:\/\/doi.org\/10.1186\/s40425-018-0393-z\n                    \n                  .","journal-title":"J Immunother Cancer"},{"key":"748_CR7","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1093\/annonc\/mdw558","volume":"28","author":"L Spain","year":"2017","unstructured":"Spain L, Walls G, Julve M, O'Meara K, Schmid T, Kalaitzaki E, Turajlic S, Gore M, Rees J, Larkin J. Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature. Ann Oncol. 2017;28:377\u201385. \n                    https:\/\/doi.org\/10.1093\/annonc\/mdw558\n                    \n                  .","journal-title":"Ann Oncol"},{"key":"748_CR8","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1001\/jamaneurol.2017.1912","volume":"74","author":"JC Kao","year":"2017","unstructured":"Kao JC, Liao B, Markovic SN, Klein CJ, Naddaf E, Staff NP, Liewluck T, Hammack JE, Sandroni P, Finnes H, Mauermann ML. Neurological complications associated with anti-programmed death 1 (PD-1) antibodies. JAMA Neurol. 2017;74:1216\u201322. \n                    https:\/\/doi.org\/10.1001\/jamaneurol.2017.1912\n                    \n                  .","journal-title":"JAMA Neurol"},{"key":"748_CR9","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1097\/wco.0000000000000391","volume":"29","author":"AF Hottinger","year":"2016","unstructured":"Hottinger AF. Neurologic complications of immune checkpoint inhibitors. Curr Opin Neurol. 2016;29:806\u201312. \n                    https:\/\/doi.org\/10.1097\/wco.0000000000000391\n                    \n                  .","journal-title":"Curr Opin Neurol"},{"key":"748_CR10","doi-asserted-by":"publisher","first-page":"2002","DOI":"10.1212\/WNL.0b013e3181a92b52","volume":"72","author":"V Iodice","year":"2009","unstructured":"Iodice V, Kimpinski K, Vernino S, Sandroni P, Fealey RD, Low PA. Efficacy of immunotherapy in seropositive and seronegative putative autoimmune autonomic ganglionopathy. Neurology. 2009;72:2002\u20138. \n                    https:\/\/doi.org\/10.1212\/WNL.0b013e3181a92b52\n                    \n                  .","journal-title":"Neurology"},{"key":"748_CR11","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.jneuroim.2018.03.018","volume":"319","author":"B Tijero","year":"2018","unstructured":"Tijero B, Del Pino R, Perez-Concha T, Acera MA, Gabilondo I, Berganzo K, Graus F, Martinez-Alday JD, Barcena J, Gomez-Esteban JC. Seronegative and seropositive autoimmune autonomic ganglionopathy (AAG): same clinical picture, same response to immunotherapy. J Neuroimmunol. 2018;319:68\u201370. \n                    https:\/\/doi.org\/10.1016\/j.jneuroim.2018.03.018\n                    \n                  .","journal-title":"J Neuroimmunol"},{"key":"748_CR12","doi-asserted-by":"publisher","first-page":"174","DOI":"10.14694\/EdBook_AM.2012.32.174","volume-title":"American Society of Clinical Oncology educational book American Society of Clinical Oncology Annual Meeting","author":"JS Weber","year":"2012","unstructured":"Weber JS. Practical management of immune-related adverse events from immune checkpoint protein antibodies for the oncologist. In: American Society of Clinical Oncology educational book American Society of Clinical Oncology Annual Meeting; 2012. p. 174\u20137. \n                    https:\/\/doi.org\/10.14694\/EdBook_AM.2012.32.174\n                    \n                  ."},{"key":"748_CR13","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1097\/CJI.0b013e318193a206","volume":"32","author":"S Bhatia","year":"2009","unstructured":"Bhatia S, Huber BR, Upton MP, Thompson JA. Inflammatory enteric neuropathy with severe constipation after ipilimumab treatment for melanoma: a case report. J Immunother. 2009;32:203\u20135. \n                    https:\/\/doi.org\/10.1097\/CJI.0b013e318193a206\n                    \n                  .","journal-title":"J Immunother"},{"key":"748_CR14","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1097\/CJI.0b013e31827807dd","volume":"36","author":"C Gaudy-Marqueste","year":"2013","unstructured":"Gaudy-Marqueste C, Monestier S, Franques J, Cantais E, Richard MA, Grob JJ. A severe case of ipilimumab-induced guillain-barre syndrome revealed by an occlusive enteric neuropathy: a differential diagnosis for ipilimumab-induced colitis. J Immunother. 2013;36:77\u20138. \n                    https:\/\/doi.org\/10.1097\/CJI.0b013e31827807dd\n                    \n                  .","journal-title":"J Immunother"},{"key":"748_CR15","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.ejca.2017.05.041","volume":"82","author":"D Makarious","year":"2017","unstructured":"Makarious D, Horwood K, Coward JIG. Myasthenia gravis: an emerging toxicity of immune checkpoint inhibitors. Eur J Cancer. 2017;82:128\u201336. \n                    https:\/\/doi.org\/10.1016\/j.ejca.2017.05.041\n                    \n                  .","journal-title":"Eur J Cancer"},{"key":"748_CR16","doi-asserted-by":"publisher","first-page":"e1702","DOI":"10.7759\/cureus.1702","volume":"9","author":"JJ Mehta","year":"2017","unstructured":"Mehta JJ, Maloney E, Srinivasan S, Seitz P, Cannon M. Myasthenia gravis induced by nivolumab: a case report. Cureus. 2017;9:e1702. \n                    https:\/\/doi.org\/10.7759\/cureus.1702\n                    \n                  .","journal-title":"Cureus"},{"key":"748_CR17","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1093\/jjco\/hyv158","volume":"46","author":"T Shirai","year":"2016","unstructured":"Shirai T, Sano T, Kamijo F, Saito N, Miyake T, Kodaira M, Katoh N, Nishie K, Okuyama R, Uhara H. Acetylcholine receptor binding antibody-associated myasthenia gravis and rhabdomyolysis induced by nivolumab in a patient with melanoma. Jpn J Clin Oncol. 2016;46:86\u20138. \n                    https:\/\/doi.org\/10.1093\/jjco\/hyv158\n                    \n                  .","journal-title":"Jpn J Clin Oncol"},{"key":"748_CR18","doi-asserted-by":"publisher","first-page":"e7350","DOI":"10.1097\/md.0000000000007350","volume":"96","author":"YH Chen","year":"2017","unstructured":"Chen YH, Liu FC, Hsu CH, Chian CF. Nivolumab-induced myasthenia gravis in a patient with squamous cell lung carcinoma: case report. Medicine. 2017;96:e7350. \n                    https:\/\/doi.org\/10.1097\/md.0000000000007350\n                    \n                  .","journal-title":"Medicine"},{"key":"748_CR19","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1634\/theoncologist.2016-0487","volume":"22","author":"J Larkin","year":"2017","unstructured":"Larkin J, Chmielowski B, Lao CD, Hodi FS, Sharfman W, Weber J, Suijkerbuijk KPM, Azevedo S, Li H, Reshef D, Avila A, Reardon DA. Neurologic serious adverse events associated with nivolumab plus ipilimumab or nivolumab alone in advanced melanoma, including a case series of encephalitis. Oncologist. 2017;22:709\u201318. \n                    https:\/\/doi.org\/10.1634\/theoncologist.2016-0487\n                    \n                  .","journal-title":"Oncologist"},{"key":"748_CR20","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.autneu.2008.09.005","volume":"146","author":"S Vernino","year":"2009","unstructured":"Vernino S, Hopkins S, Wang Z. Autonomic ganglia, acetylcholine receptor antibodies, and autoimmune ganglionopathy. Auton Neurosci. 2009;146:3\u20137. \n                    https:\/\/doi.org\/10.1016\/j.autneu.2008.09.005\n                    \n                  .","journal-title":"Auton Neurosci"},{"key":"748_CR21","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1097\/WCO.0b013e32833d4c7f","volume":"23","author":"N Winston","year":"2010","unstructured":"Winston N, Vernino S. Recent advances in autoimmune autonomic ganglionopathy. Curr Opin Neurol. 2010;23:514\u20138. \n                    https:\/\/doi.org\/10.1097\/WCO.0b013e32833d4c7f\n                    \n                  .","journal-title":"Curr Opin Neurol"},{"key":"748_CR22","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.autneu.2009.06.002","volume":"150","author":"K Kimpinski","year":"2009","unstructured":"Kimpinski K, Iodice V, Vernino S, Sandroni P, Low PA. Association of N-type calcium channel autoimmunity in patients with autoimmune autonomic ganglionopathy. Auton Neurosci. 2009;150:136\u20139. \n                    https:\/\/doi.org\/10.1016\/j.autneu.2009.06.002\n                    \n                  .","journal-title":"Auton Neurosci"},{"key":"748_CR23","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.autneu.2008.10.022","volume":"146","author":"P Sandroni","year":"2009","unstructured":"Sandroni P, Low PA. Other autonomic neuropathies associated with ganglionic antibody. Auton Neurosci. 2009;146:13\u20137. \n                    https:\/\/doi.org\/10.1016\/j.autneu.2008.10.022\n                    \n                  .","journal-title":"Auton Neurosci"},{"key":"748_CR24","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.autneu.2008.11.001","volume":"146","author":"V Iodice","year":"2009","unstructured":"Iodice V, Kimpinski K, Vernino S, Sandroni P, Low PA. Immunotherapy for autoimmune autonomic ganglionopathy. Auton Neurosci. 2009;146:22\u20135. \n                    https:\/\/doi.org\/10.1016\/j.autneu.2008.11.001\n                    \n                  .","journal-title":"Auton Neurosci"},{"key":"748_CR25","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1007\/s12254-018-0416-y","volume":"11","author":"JD Rudzki","year":"2018","unstructured":"Rudzki JD. Management of adverse events related to checkpoint inhibition therapy. Memo. 2018;11:132\u20137. \n                    https:\/\/doi.org\/10.1007\/s12254-018-0416-y\n                    \n                  .","journal-title":"Memo"},{"key":"748_CR26","doi-asserted-by":"publisher","first-page":"iv264","DOI":"10.1093\/annonc\/mdy162","volume":"29","author":"J Haanen","year":"2018","unstructured":"Haanen J, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, Jordan K. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29:iv264\u20136. \n                    https:\/\/doi.org\/10.1093\/annonc\/mdy162\n                    \n                  .","journal-title":"Ann Oncol"},{"key":"748_CR27","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s10286-017-0493-8","volume":"28","author":"EP Golden","year":"2018","unstructured":"Golden EP, Bryarly MA, Vernino S. Seronegative autoimmune autonomic neuropathy: a distinct clinical entity. Clin Auton Res. 2018;28:115\u201323. \n                    https:\/\/doi.org\/10.1007\/s10286-017-0493-8\n                    \n                  .","journal-title":"Clin Auton Res"},{"key":"748_CR28","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1097\/cji.0000000000000167","volume":"40","author":"W Kelly Wu","year":"2017","unstructured":"Kelly Wu W, Broman KK, Brownie ER, Kauffmann RM. Ipilimumab-induced Guillain-Barre syndrome presenting as dysautonomia: an unusual presentation of a rare complication of immunotherapy. J Immunother. 2017;40:196\u20139. \n                    https:\/\/doi.org\/10.1097\/cji.0000000000000167\n                    \n                  .","journal-title":"J Immunother"},{"key":"748_CR29","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1002\/mus.23830","volume":"48","author":"G Manousakis","year":"2013","unstructured":"Manousakis G, Koch J, Sommerville RB, El-Dokla A, Harms MB, Al-Lozi MT, Schmidt RE, Pestronk A. Multifocal radiculoneuropathy during ipilimumab treatment of melanoma. Muscle Nerve. 2013;48:440\u20134. \n                    https:\/\/doi.org\/10.1002\/mus.23830\n                    \n                  .","journal-title":"Muscle Nerve"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40425-019-0748-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s40425-019-0748-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40425-019-0748-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T17:45:24Z","timestamp":1601055924000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1186\/s40425-019-0748-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,17]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["748"],"URL":"https:\/\/doi.org\/10.1186\/s40425-019-0748-0","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,17]]},"assertion":[{"value":"16 April 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 September 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Patient is deceased.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"262"}}