Autoimmune Autonomic Neuropathy: From Pathogenesis to Diagnosis.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Autoimmune Diseases of the Nervous System* ; Autonomic Nervous System Diseases*/diagnosis ; Autonomic Nervous System Diseases*/etiology ; Autoimmune Diseases*/diagnosis ; Autoimmune Diseases*/pathology ; Peripheral Nervous System Diseases*/pathology; Humans ; Ganglia, Autonomic ; Post-Acute COVID-19 Syndrome ; Autonomic Nervous System ; Autoantibodies

Autoimmune autonomic ganglionopathy (AAG) is a disease of autonomic failure caused by ganglionic acetylcholine receptor (gAChR) autoantibodies. Although the detection of autoantibodies is important for distinguishing the disease from other neuropathies that present with autonomic dysfunction, other factors are important for accurate diagnosis. Here, we provide a comprehensive review of the clinical features of AAG, highlighting differences in clinical course, clinical presentation, and laboratory findings from other neuropathies presenting with autonomic symptoms. The first step in diagnosing AAG is careful history taking, which should reveal whether the mode of onset is acute or chronic, followed by an examination of the time course of disease progression, including the presentation of autonomic and extra-autonomic symptoms. AAG is a neuropathy that should be differentiated from other neuropathies when the patient presents with autonomic dysfunction. Immune-mediated neuropathies, such as acute autonomic sensory neuropathy, are sometimes difficult to differentiate, and therefore, differences in clinical and laboratory findings should be well understood. Other non-neuropathic conditions, such as postural orthostatic tachycardia syndrome, chronic fatigue syndrome, and long COVID, also present with symptoms similar to those of AAG. Although often challenging, efforts should be made to differentiate among the disease candidates.

Brain Dev. 2016 Jun;38(6):605-8. (PMID: 26740077)
Pract Neurol. 2022 Feb;22(1):19-31. (PMID: 34510016)
Neurocrit Care. 2020 Feb;32(1):113-120. (PMID: 31297663)
Pediatr Int. 2015;57(1):30-6. (PMID: 25422087)
Rinsho Shinkeigaku. 2009 Sep;49(9):582-5. (PMID: 19928689)
J Neurol Neurosurg Psychiatry. 2017 Apr;88(4):367-368. (PMID: 27837100)
Rheumatology (Oxford). 2002 May;41(5):586-8. (PMID: 12011386)
Orphanet J Rare Dis. 2018 Jan 17;13(1):6. (PMID: 29343286)
Autoimmun Rev. 2022 May;21(5):103071. (PMID: 35182777)
Arthritis Rheum. 2005 Oct;52(10):2984-95. (PMID: 16200578)
Front Immunol. 2021 Jul 26;12:702505. (PMID: 34381453)
Autoimmun Rev. 2009 Jun;8(7):569-72. (PMID: 19393212)
Curr Treat Options Neurol. 2020;22(11):37. (PMID: 32994698)
Respir Med. 2017 May;126:135-138. (PMID: 28318820)
Ann Clin Transl Neurol. 2018 Feb 28;5(4):486-492. (PMID: 29687025)
Sci Rep. 2023 May 22;13(1):8251. (PMID: 37217645)
Auton Neurosci. 2009 Mar 12;146(1-2):26-8. (PMID: 19195935)
Curr Neurol Neurosci Rep. 2019 Jun 20;19(8):52. (PMID: 31222456)
Handb Clin Neurol. 2013;115:893-906. (PMID: 23931820)
Brain. 2010 Oct;133(10):2881-96. (PMID: 20736188)
J Neurol. 2022 Sep;269(9):4611-4612. (PMID: 35536408)
J Immunol Methods. 2021 Nov;498:113124. (PMID: 34425081)
J Neurol. 2021 Nov;268(11):4265-4279. (PMID: 33881596)
Ann Clin Transl Neurol. 2021 Apr;8(4):790-799. (PMID: 33621398)
Lancet Neurol. 2009 Jul;8(7):654-67. (PMID: 19539237)
J Cardiovasc Dev Dis. 2021 Nov 15;8(11):. (PMID: 34821709)
Nat Commun. 2022 Mar 9;13(1):1220. (PMID: 35264564)
Intern Med. 2018 Jan 15;57(2):181-187. (PMID: 29093404)
Mod Rheumatol. 2013 Sep;23(5):841-5. (PMID: 23135882)
Handb Clin Neurol. 2014;126:63-79. (PMID: 25410215)
Neurol Neuroimmunol Neuroinflamm. 2022 Mar 29;9(3):. (PMID: 35351814)
Intern Med. 2015;54(15):1919-22. (PMID: 26234237)
Muscle Nerve. 2022 Apr;65(4):440-443. (PMID: 34766365)
Muscle Nerve. 2006 Jan;33(1):78-84. (PMID: 16184605)
Int J Rheum Dis. 2022 Nov;25(11):1246-1253. (PMID: 35915515)
Autoimmun Rev. 2007 Jan;6(3):162-8. (PMID: 17289552)
J Transl Autoimmun. 2021;4:100100. (PMID: 33880442)
J Auton Nerv Syst. 1990 Jul;30 Suppl:S179-84. (PMID: 2212485)
Pract Neurol. 2020 May;20(3):199-212. (PMID: 32424017)
Brain Behav Immun Health. 2023 Mar;28:100578. (PMID: 36686624)
Neurol Neuroimmunol Neuroinflamm. 2021 Oct 4;8(6):. (PMID: 34607912)
Nat Rev Neurol. 2014 Jul;10(7):396-407. (PMID: 24866874)
Clin Neurophysiol. 2003 Sep;114(9):1609-14. (PMID: 12948789)
J Neurol. 2022 Feb;269(2):587-596. (PMID: 34386903)
Clin Auton Res. 2019 Jun;29(3):289-299. (PMID: 30019292)
PLoS One. 2015 Mar 19;10(3):e0118312. (PMID: 25790156)
Clin Auton Res. 2021 Jun;31(3):385-394. (PMID: 33860871)
No To Hattatsu. 1995 Jan;27(1):41-6. (PMID: 7873251)
Auton Neurosci. 2023 Mar;245:103070. (PMID: 36634383)
Methodist Debakey Cardiovasc J. 2018 Oct-Dec;14(4):251-256. (PMID: 30788010)
Clin Auton Res. 2019 Sep;29(Suppl 1):33-44. (PMID: 31452021)
Nat Rev Neurol. 2012 Jan 24;8(2):73-85. (PMID: 22270030)
CEN Case Rep. 2016 May;5(1):5-10. (PMID: 28509159)
Neurology. 2005 Jul 12;65(1):138-40. (PMID: 16009902)
Neurology. 1998 Jun;50(6):1806-13. (PMID: 9633732)
Neurol Neuroimmunol Neuroinflamm. 2022 Mar 1;9(3):. (PMID: 35232750)
Auton Neurosci. 2009 Mar 12;146(1-2):3-7. (PMID: 18951069)
Neurology. 2008 May 13;70(20):1926-32. (PMID: 18474849)
Muscle Nerve. 2022 Jun;65(6):E31-E32. (PMID: 35385125)
Clin Exp Immunol. 1997 Dec;110(3):423-7. (PMID: 9409646)
J Autoimmun. 2020 Mar;108:102403. (PMID: 31924415)
Ann Neurol. 2015 Aug;78(2):272-83. (PMID: 25973863)
Eur J Neurol. 2023 May;30(5):1528-1539. (PMID: 36694382)
Neurol Sci. 2023 Sep;44(9):3071-3082. (PMID: 37083958)
Diabetes Care. 2003 May;26(5):1553-79. (PMID: 12716821)
Immunol Res. 2021 Apr;69(2):205-211. (PMID: 33786700)
Clin Auton Res. 2019 Sep;29(Suppl 1):25-31. (PMID: 31506870)
J Clin Pathol. 2023 Jan;76(1):19-28. (PMID: 36270794)
Lupus. 2007;16(3):181-5. (PMID: 17432103)
J Clin Invest. 2003 Mar;111(6):907-13. (PMID: 12639997)
Diabetes Obes Metab. 2023 May;25(5):1162-1173. (PMID: 36748121)
Clin Auton Res. 2019 Sep;29(Suppl 1):55-63. (PMID: 31452022)
Front Neurosci. 2022 Nov 23;16:1006923. (PMID: 36507326)
Curr Opin Neurol. 2006 Oct;19(5):474-80. (PMID: 16969157)
J Neurophysiol. 2003 Sep;90(3):2053-9. (PMID: 12773498)
Autoimmun Rev. 2023 Sep;22(9):103402. (PMID: 37490975)
Ann Rheum Dis. 2012 Dec;71(12):1973-9. (PMID: 22562982)
Arch Neurol. 2012 Apr;69(4):461-6. (PMID: 22158721)
Mayo Clin Proc. 2012 Dec;87(12):1196-201. (PMID: 23218087)
Diab Vasc Dis Res. 2008 Nov;5(4):336-44. (PMID: 18958844)
Auton Neurosci. 2020 Dec;229:102718. (PMID: 32916479)
Auton Neurosci. 2009 Mar 12;146(1-2):29-32. (PMID: 19028442)
JCI Insight. 2019 Apr 18;4(8):. (PMID: 30996138)
J Neurosci. 2004 Aug 11;24(32):7037-42. (PMID: 15306637)
Rinsho Shinkeigaku. 1998 Jul;38(7):663-8. (PMID: 9868313)
J Rheumatol. 2007 Sep;34(9):1869-74. (PMID: 17659755)
J Clin Neurosci. 2017 May;39:90-92. (PMID: 28214088)
Lancet. 2005 Apr 2-8;365(9466):1259-70. (PMID: 15811460)
Neurology. 2007 May 29;68(22):1917-21. (PMID: 17536048)
Clin Genet. 2017 Dec;92(6):659-663. (PMID: 28422281)
N Engl J Med. 2018 Jul 5;379(1):11-21. (PMID: 29972753)
J Neurol Neurosurg Psychiatry. 2013 Jan;84(1):98-106. (PMID: 22906617)
Rinsho Shinkeigaku. 1989 Oct;29(10):1265-71. (PMID: 2557996)
Clin Auton Res. 2002 Apr;12(2):84-7. (PMID: 12102455)
Lancet Neurol. 2008 Oct;7(10):939-50. (PMID: 18848313)
Neurology. 2009 Jun 9;72(23):2002-8. (PMID: 19506222)
Neurology. 2012 Mar 6;78(10):702-8. (PMID: 22357716)
Auton Neurosci. 2023 Mar;245:103071. (PMID: 36580747)
Int J Environ Res Public Health. 2021 May 17;18(10):. (PMID: 34067776)
Mod Rheumatol. 2016 Sep;26(5):708-15. (PMID: 26873295)
Front Immunol. 2021 Jun 23;12:705292. (PMID: 34249013)
Int J Mol Sci. 2022 Apr 12;23(8):. (PMID: 35457093)
Transl Neurodegener. 2014 Sep 13;3:19. (PMID: 25228988)
Europace. 2017 Jul 01;19(7):1211-1219. (PMID: 27702852)
Mod Rheumatol. 2017 Jul;27(4):664-668. (PMID: 27538899)
Neuromolecular Med. 2006;8(1-2):147-58. (PMID: 16775373)
J Am Heart Assoc. 2014 Feb 26;3(1):e000755. (PMID: 24572257)
Clin Auton Res. 2021 Jun;31(3):365-368. (PMID: 33740207)
J Clin Invest. 2006 Nov;116(11):2843-54. (PMID: 17080188)
Pharmacol Res. 2023 Jun;192:106790. (PMID: 37164280)
Lupus. 2007;16(9):767-8. (PMID: 17728374)
Clin Med (Lond). 2021 Jan;21(1):e63-e67. (PMID: 33243837)
Front Neurol. 2022 May 27;13:886609. (PMID: 35720084)
Arch Neurol. 2002 Nov;59(11):1771-6. (PMID: 12433265)
Neurology. 2009 Nov 3;73(18):1501-6. (PMID: 19884578)
Clin Exp Nephrol. 2009 Apr;13(2):152-155. (PMID: 19153803)
Kidney Int. 1999 Jul;56(1):232-7. (PMID: 10411697)
Nat Med. 2021 Apr;27(4):601-615. (PMID: 33753937)
Int J Mol Sci. 2020 Feb 16;21(4):. (PMID: 32079137)
N Engl J Med. 2000 Sep 21;343(12):847-55. (PMID: 10995864)
Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1245-50. (PMID: 22128336)
Orphanet J Rare Dis. 2007 Oct 03;2:39. (PMID: 17915006)
Auton Neurosci. 2009 Mar 12;146(1-2):18-21. (PMID: 19155193)

22FC1007 Ministry of Health Labour and Welfare

Keywords: autoantibodies; autoimmune autonomic ganglionopathy; extra-autonomic manifestations; ganglionic acetylcholine receptor; immunotherapy

0 (Autoantibodies)

Date Created: 20240224 Date Completed: 20240226 Latest Revision: 20240227

20240227

PMC10889307

10.3390/ijms25042296

38396973