Skip to main content
SpringerLink
Log in

Autoantibody Testing in the Diagnosis and Management of Autoimmune Disorders of Neuromuscular Transmission and Related Diseases

  • Chapter
  • First Online:
Myasthenia Gravis and Related Disorders

Part of the book series: Current Clinical Neurology ((CCNEU))

Abstract

The neuromuscular junction is the site of at least three distinct antibody-mediated diseases, myasthenia gravis (MG), the Lambert-Eaton myasthenic syndrome (LEMS), and acquired neuromyotonia. Antibodies to AChR and MuSK can be helpful in the diagnosis of myasthenia gravis, and their detection in patients with neuromuscular transmission disorders has helped define new subtypes of the disease. With increasing reluctance to use the classical radioimmunoprecipitation assays, other techniques such as ELISA and cell-based assays (CBAs) have been established; CBAs have also been used to detect antibodies to LRP4, agrin and other antigens, in some otherwise negative MG patients, but the roles of these antibodies are not clear yet. Antibodies to VGCC in the Lambert-Eaton myasthenic syndrome and to the VGKC-complex proteins, CASPR2 and LGI1, in acquired neuromyotonia are becoming more widely available. Although often helpful, these methods still need to be validated and standardized. Moreover, although each of these antibodies has the potential to be pathogenic, since they bind to extracellular aspects of membrane proteins, the pathogenic mechanisms need further studies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Patrick J, Lindstrom J. Autoimmune response to acetylcholine receptor. Science. 1973;180:871–2.

    Article  CAS  PubMed  Google Scholar 

  2. Fambrough DM, Drachman DB, Satyamurti S.Neuromuscular junction in myasthenia gravis: decreased acetylcholine receptors. Science. 1973;182:293–5.

    Article  CAS  PubMed  Google Scholar 

  3. Lindstrom JM, Seybold ME, Lennon VA, Whittingham S, Duane DD. Antibody to acetylcholine receptor in myasthenia gravis: prevalence, clinical correlates, and diagnostic value. Neurology. 1976;26:1054–9.

    Article  CAS  PubMed  Google Scholar 

  4. Toyka KV, Drachman DB, Griffin DE, Pestronk A, Winkelstein JA, Fishbeck KH, et al. Myasthenia gravis: study of humoral immune mechanisms by passive transfer to mice. N Engl J Med. 1977;296:125–31.

    Article  CAS  PubMed  Google Scholar 

  5. Pinching AJ, Peters DK, Newsom-Davis JN.Remission of myasthenia gravis following plasma exchange. Lancet. 1976;2:1373–6.

    Article  CAS  PubMed  Google Scholar 

  6. Viegas S, Jacobson L, Waters P, Cossins J, Jacob S, Leite MI, et al. Passive and active immunization models of MuSK-Ab positive myasthenia: electrophysiological evidence for pre and postsynaptic defects. Exp Neurol. 2012;234(2):506–12.

    Article  CAS  PubMed  Google Scholar 

  7. Lang B, Newsom-Davis J, Prior C, Wray D. Antibodies to motor nerve terminals: an electrophysiological study of a human myasthenic syndrome transferred to a mouse. J Physiol Lond. 1983;344:335–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Shillito P, Molenaar PC, Vincent A, Leys K, Zheng W, van den Berg RJ, et al. Acquired neuromyotonia: evidence for vie autoantibodies directed against K+ channels of peripheral nerves. Ann Neurol. 1995;38(5):714–22.

    Article  CAS  PubMed  Google Scholar 

  9. Mossman S, Vincent A, Newsom-Davis J. Passive transfer of myasthenia gravis by immunoglobulins: lack of correlation between antibody bound, acetylcholine receptor loss and transmission defect. J Neurol Sci. 1988;84:15–28.

    Article  CAS  PubMed  Google Scholar 

  10. Compston DA, Vincent A, Newsom-Davis J, Batchelor JR. Clinical, pathological, HLA antigen and immunological evidence for disease heterogeneity in myasthenia gravis. Brain. 1980;103:579–601.

    Article  CAS  PubMed  Google Scholar 

  11. Guptill JT, Sanders DB, Evoli A. Anti-MuSK-Ab myasthenia gravis: clinical findings and response to treatment in two large cohorts. Muscle Nerve. 2011;44:36–40.

    Article  PubMed  Google Scholar 

  12. Evoli A, Tonali PA, Padua L, Monaco ML, Scuderi F, Batocchi AP, et al. Clinical correlates with anti-MuSK-Abs in generalized seronegative myasthenia gravis. Brain. 2003;126:2304–11.

    Article  PubMed  Google Scholar 

  13. Pasnoor M, Wolfe GI, Nations S, Trivedi J, Barohn RJ, Herbelin L, et al. Clinical findings in MuSK-antibody positive myasthenia gravis: a U.S. experience. Muscle Nerve. 2010;41:370–4.

    Article  PubMed  Google Scholar 

  14. Skjei KL, Lennon VA, Kuntz NL. Muscle specific kinase autoimmune myasthenia gravis in children: a case series. Neuromuscul Disord. 2013;23:874–82.

    Article  PubMed  Google Scholar 

  15. Evoli A. Clinical aspects of neuromuscular transmission disorders. Acta Neurol Scand Suppl. 2006;183:8–11. Review.

    Article  PubMed  Google Scholar 

  16. Marx A, Pfister F, Schalke B, Saruhan-Direskeneli G, Melms A, Ströbel P. The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev. 2013;12:875–84.

    Article  CAS  PubMed  Google Scholar 

  17. Higuchi O, Hamuro J, Motomura M, Yamanashi Y. Autoantibodies to low-density lipoprotein receptor-related protein 4 in myasthenia gravis. Ann Neurol. 2011;69:418–22.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang B, Tzartos JS, Belimezi M, Ragheb S, Bealmear B, Lewis RA, et al. Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis. Arch Neurol. 2012;69:445–51.

    Article  PubMed  Google Scholar 

  19. Pevzner A, Schoser B, Peters K, Cosma NC, Karakatsani A, Schalke B, et al. Anti-LRP4 autoantibodies in AChR- and MuSK-antibody-negative myasthenia gravis. J Neurol. 2012;259:427–35.

    Article  CAS  PubMed  Google Scholar 

  20. Zisimopoulou P, Evangelakou P, Tzartos J, Lazaridis K, Zouvelou V, Mantegazza R, et al. A comprehensive analysis of the epidemiology and clinical characteristics of anti-LRP4 in myasthenia gravis. J Autoimmun. 2014;52:139–45.

    Article  CAS  PubMed  Google Scholar 

  21. Newsom-Davis J, Pinching AJ, Vincent A, Wilson SG. Function of circulating antibody to acetylcholine receptor in myasthenia gravis: investigated by plasma exchange. Neurology. 1978;28:266–72.

    Article  CAS  PubMed  Google Scholar 

  22. Dau PC. Plasmpheresis therapy in myasthenia gravis. Muscle Nerve. 1980;3:468–82.

    Article  CAS  PubMed  Google Scholar 

  23. Oosterhuis HJGH, Limburg PC, Hummel-Tappel E. Anti-acetylcholine receptor antibodies in myasthenia gravis. Part 2. Clinical and serological follow-up of individual patients. J Neurol Sci. 1983;58:371–85.

    Article  CAS  PubMed  Google Scholar 

  24. Tzartos SJ, Loutrari HV, Tang F, Kokla A, Walgrave SL, Milius RP, et al. Main immunogenic region of torpedo electroplax and human muscle acetylcholine receptor: localization and microheterogeneity revealed by the use of synthetic peptides. J Neurochem. 1990;54:51–61.

    Article  CAS  PubMed  Google Scholar 

  25. Lennon VA, Seybold ME, Lindstrom JM, Cochrane C, Ulevitch R. Role of complement in the pathogenesis of experimental autoimmune myasthenia gravis. J Exp Med. 1978;147:973–83.

    Article  CAS  PubMed  Google Scholar 

  26. Gomez CM, Richman DP. Chronic experimental autoimmune myasthenia gravis induced by monoclonal antibody to acetylcholine receptor: biochemical and electrophysiological criteria. J Immunol. 1987;139:73–6.

    CAS  PubMed  Google Scholar 

  27. Maselli RA, Richman DP, Wollmann RL.Inflammation at the neuromuscular junction in myasthenia gravis. Neurology. 1991;41:1497–504.

    Article  CAS  PubMed  Google Scholar 

  28. Drachman DB, Adams RN, Josifek LF, Self SG. Functional activities of autoantibodies to acetylcholine receptors and the clinical severity of myasthenia gravis. N Engl J Med. 1982;307:769–75.

    Article  CAS  PubMed  Google Scholar 

  29. Howard FM, Lennon VA, Finley J, Matsumoto J, Elveback LR. Clinical correlations of antibodies that bind, block or modulate human acetylcholine receptors in myasthenia gravis. Ann N Y Acad Sci. 1987;505:526–38.

    Article  PubMed  Google Scholar 

  30. Hubbard SR, Gnanasambandan K. Structure and activation of MuSK, a receptor tyrosine kinase central to neuromuscular junction formation. Biochim Biophys Acta. 2013;1834:2166–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Darabid H, Perez-Gonzalez AP, Robitaille R.Neuromuscular synaptogenesis: coordinating partners with multiple functions. Nat Rev Neurosci. 2014;15:703–18. Review.

    Article  CAS  PubMed  Google Scholar 

  32. Blaes F, Beeson D, Plested P, Lang B, Vincent A. IgG from “seronegative” myasthenia gravis patients binds to a muscle cell line, TE671, but not to human acetylcholine receptor. Ann Neurol. 2000;47:504–10.

    Article  CAS  PubMed  Google Scholar 

  33. Hoch W, McConville J, Helms S, Newsom-Davis J, Melms A, Vincent A. Autoantibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med. 2001;7:365–8.

    Article  CAS  PubMed  Google Scholar 

  34. McConville J, Farrugia ME, Beeson D, Kishore U, Metcalfe R, Newsom-Davis J, et al. Detection and characterization of MuSK-Abs in seronegative myasthenia gravis. Ann Neurol. 2004;55(4):580–4.

    Article  CAS  PubMed  Google Scholar 

  35. Koneczny I, Stevens JA, De Rosa A, Huda S, Huijbers MG, Saxena A, et al. IgG4 autoantibodies against muscle-specific kinase undergo Fab-arm exchange in myasthenia gravis patients. J Autoimmun. 2017;77:104–15.

    Article  CAS  PubMed  Google Scholar 

  36. Shigemoto K, Kubo S, Maruyama N, Hato N, Yamada H, Jie C, et al. Induction of myasthenia by immunization against muscle-specific kinase. J Clin Invest. 2006;116:1016–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cole RN, Ghazanfari N, Ngo ST, Gervásio OL, Reddel SW, Phillips WD. Patient autoantibodies deplete postsynaptic muscles-pecific kinase leading to disassembly of the ACh receptor scaffold and myasthenia gravis in mice. J Physiol. 2010;588:3217–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Klooster R, Plomp JJ, Huijbers MG, Niks EH, Straasheijm KR, Detmers FJ, et al. Muscle-specific kinase myasthenia gravis IgG4 autoantibodies cause severe neuromuscular junction dysfunction in mice. Brain. 2012;135:1081–101.

    Article  PubMed  Google Scholar 

  39. Koneczny I, Cossins J, Waters P, Beeson D, Vincent A. MuSK myasthenia gravis IgG4 disrupts the interaction of LRP4 with MuSK but both IgG4 and IgG1-3 can disperse preformed agrin-independent AChR clusters. PLoS One. 2013;8:e80695.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Huijbers MG, Zhang W, Klooster R, et al. MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between MuSK and LRP4. Proc Natl Acad Sci U S A. 2013;110:20783–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Küçükerden M, Huda R, Tüzün E, Yılmaz A, Skriapa L, Trakas N, et al. MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK. J Neuroimmunol. 2016;295–296:84–92.

    Article  PubMed  Google Scholar 

  42. Mori S, Kubo S, Akiyoshi T, Yamada S, Miyazaki T, Hotta H, et al. Antibodies against muscle specific kinase impair both presynaptic and postsynaptic functions in a murine model of myasthenia gravis. Am J Pathol. 2012;180:798–810.

    Article  CAS  PubMed  Google Scholar 

  43. Patel V, Oh A, Voit A, Sultatos LG, Babu GJ, Wilson BA, et al. Altered active zones, vesicle pools, nerve terminal conductivity,and morphology during experimental MuSK myasthenia gravis. PLoS One. 2014;9:e110571.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Shen C, Lu Y, Zhang B, Figueiredo D, Figueiredo D, Bean J, Jung J, et al. Antibodies against low-density lipoprotein receptor-related protein 4 induce myasthenia gravis. J Clin Invest. 2013;123:5190–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Vincent A, Newsom-Davis J. Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. J Neurol Neurosurg Psychiatry. 1985;48:1246–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kaminski HJ. Acetylcholine receptor epitopes in ocular myasthenia. Ann N Y Acad Sci. 1998;841:309–19.

    Article  CAS  PubMed  Google Scholar 

  47. Matthews I, Chen S, Hewer R, McGrath V, Furmaniak J, Rees Smith B. Muscle-specific receptor tyrosine kinase autoantibodies—a new immunoprecipitation assay. Clin Chim Acta. 2004;348:95–9.

    Article  CAS  PubMed  Google Scholar 

  48. Niks EH, Kuks JB, Roep BO, Haasnoot GW, Verduijn W, Ballieux BE, et al. Strong association of MuSK antibody-positive myasthenia gravis and HLA-DR14-DQ5. Neurology. 2006;66:1772–4.

    Article  CAS  PubMed  Google Scholar 

  49. Lang B, Richardson G, Rees J, Vincent A, Newsom-Davis J. Plasma from myasthenia gravis patients reduces acetylcholine receptor agonist-induced Na+ flux into TE671 cell line. J Neuroimmunol. 1988;19:141–8.

    Article  CAS  PubMed  Google Scholar 

  50. Bufler J, Pitz R, Czep M, Wick M, Franke C. Purified IgG from seropositive and seronegative patients with myasthenia gravis reversibly blocks currents through nicotinic acetylcholine receptor channels. Ann Neurol. 1998;43:458–64.

    Article  CAS  PubMed  Google Scholar 

  51. Lennon VA. Serological diagnosis of myasthenia gravis and the Lambert Eaton Myasthenic syndrome. In: Lisak RP, editor. Handbook of myasthenia gravis and myasthenic syndromes. New York: Marcel Dekker; 1994. p. 149–64.

    Google Scholar 

  52. Leite MI, Jacob S, Viegas S, Cossins J, Clover L, Morgan BP, et al. IgG1 antibodies to acetylcholine receptors in ‘seronegative’ myasthenia gravis. Brain. 2008;131:1940–52.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Jacob S, Viegas S, Leite MI, Webster R, Cossins J, Kennett R, et al. Presence and pathogenic relevance of antibodies to clustered acetylcholine receptor in ocular and generalized myasthenia gravis. Arch Neurol. 2012;69:994–1001.

    Article  PubMed  Google Scholar 

  54. Rodríguez Cruz PM, Al-Hajjar M, Jacobson L, Woodhall M, Jayawant S, et al. Clinical features and diagnostic usefulness of antibodies to clustered acetylcholine receptors in the diagnosis of seronegative myasthenia gravis. JAMA Neurol. 2015;72:642–9.

    Article  PubMed  Google Scholar 

  55. Huda S, Waters P, Woodhall M, Leite MI, Jacobson L, De Rosa A, et al. IgG-specific cell-based assay detects potentially pathogenic MuSK-Abs in seronegative MG. Neurol Neuroimmunol Neuroinflamm. 2017;4:e357.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Aarli JA, Stefansson K, Marton LSG, Wollmann RL. Patients with myasthenia gravis and thymoma have in their sera IgG autoantibodies against titin. Clin Exp Immunol. 1990;82:284–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Skeie GO, Lunde PK, Sejersted OM, Mygland A, Aarli JA, Gilhus NE. Autoimmunity against the ryanodine receptor in myasthenia gravis. Acta Physiol Scand. 2001;171:379–84.

    Article  CAS  PubMed  Google Scholar 

  58. Romi F, Skeie GO, Aarli JA, Gilhus NE. Muscle autoantibodies in subgroups of myasthenia gravis patients. J Neurol. 2000;247:369–75.

    Article  CAS  PubMed  Google Scholar 

  59. Romi F, Skeie GO, Aarli JA, Gilhus NE. The severity of myasthenia gravis correlates with the serum concentration of titin and ryanodine receptor antibodies. Arch Neurol. 2000;57:1596–600.

    Article  CAS  PubMed  Google Scholar 

  60. Mygland A, Vincent A, Newsom-Davis J, Kaminski H, Zorzato F, Agius M, et al. Autoantibodies in thymoma-associated myasthenia gravis with myositis or neuromyotonia. Arch Neurol. 2000;57:527–31.

    Article  CAS  PubMed  Google Scholar 

  61. Suzuki S, Baba A, Kaida K, Utsugisawa K, Kita Y, Tsugawa J, et al. Cardiac involvements in myasthenia gravis associated with anti-Kv1.4 antibodies. Eur J Neurol. 2014;21:223–30.

    Article  CAS  PubMed  Google Scholar 

  62. Lee E-K, Maselli RA, Ellis WG, Agius MA. Morvan’s fibrillary chorea: a paraneoplastic manifestation of thymoma. J Neurol Neurosurg Psychiatry. 1998;65:857–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Agius MA, Zhu S, Kirvan CA, Schafer AL, Lin MY, Fairclough RH, et al. Rapsyn antibodies in myasthenia gravis. Ann N Y Acad Sci. 1998;841:516–24.

    Article  CAS  PubMed  Google Scholar 

  64. Hagiwara H, Enomoto-Nakatani S, Sakai K, Ugawa Y, Kusunoki S, Kanazawa I. Stiff-person syndrome associated with invasive thymoma: a case report. Neurol Sci. 2001;193:59–62.

    Article  CAS  Google Scholar 

  65. Buckley C, Newsom-Davis J, Willcox N, Vincent A. Do titin and cytokine antibodies in MG patients predict thymoma or thymoma recurrence? Neurology. 2001;57:1579–82.

    Article  CAS  PubMed  Google Scholar 

  66. Cordts I, Bodart N, Hartmann K, Karagiorgou K, Tzartos JS, Mei L, et al. Screening for lipoprotein receptor-related protein 4-, agrin-, and titin-antibodies and exploring the autoimmune spectrum in myasthenia gravis. J Neurol. 2017;264:1193–203.

    Article  CAS  PubMed  Google Scholar 

  67. Morsch M, Reddel SW, Ghazanfari N, Toyka KV, Phillips WD. Pyridostigmine but not 3,4-diaminopyridine exacerbates ACh receptor loss and myasthenia induced in mice by muscle-specific kinase autoantibody. J Physiol. 2013;591:2747–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kerty E, Elsais A, Argov Z, Evoli A, Gilhus NE. EFNS/ENS guidelines for the treatment of ocular myasthenia gravis. Eur J Neurol. 2014;21:687–93.

    Article  CAS  PubMed  Google Scholar 

  69. Cossins J, Belaya K, Zoltowska K, Koneczny I, Maxwell S, Jacobson L, et al. The search for new antigenic targets in myasthenia gravis. Ann N Y Acad Sci. 2012;1275:123–8. Review.

    Article  CAS  PubMed  Google Scholar 

  70. Gasperi C, Melms A, Schoser B, Zhang Y, Meltoranta J, Risson V, et al. Anti-agrin autoantibodies in myasthenia gravis. Neurology. 2014;82:1976–83.

    Article  CAS  PubMed  Google Scholar 

  71. Gallardo E, Martínez-Hernández E, Titulaer MJ, Huijbers MG, Martínez MA, Ramos A, et al. Cortactin autoantibodies in myasthenia gravis. Autoimmun Rev. 2014;13:1003–7.

    Article  CAS  PubMed  Google Scholar 

  72. Zoltowska KM, Belaya K, Leite M, Patrick W, Vincent A, Beeson D. Collagen Q—a potential target for autoantibodies in myasthenia gravis. J Neurol Sci. 2015;348:241–4.

    Article  Google Scholar 

  73. Zhang B, Shen C, Bealmear B, Ragheb S, Xiong WC, Lewis RA, et al. Autoantibodies to agrin in myasthenia gravis patients. PLoS One. 2014;9:e91816.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Lennon VA, Lambert EH, Whittingham S, Fairbanks V. Autoimmunity in the Lambert-Eaton myasthenic syndrome. Muscle Nerve. 1982;5:S21–5.

    CAS  PubMed  Google Scholar 

  75. Newsom-Davis J, Murray NM. Plasma exchange and immunosuppressive drug treatment in the Lambert-Eaton myasthenic syndrome. Neurology. 1984;34:480–5.

    Article  CAS  PubMed  Google Scholar 

  76. Fukunaga H, Engel AG, Osame M, Lambert EH.Paucity and disorganization of presynaptic membrane active zones in the Lambert-Eaton myasthenic syndrome. Muscle Nerve. 1982;5:686–97.

    Article  Google Scholar 

  77. Fukuoka T, Engel AG, Lang B, Newsom-Davis J, Prior C, Wray DW. Lambert-Eaton myasthenic syndrome: I. Early morphological effects of IgG on the presynaptic membrane active zones. Ann Neurol. 1987;22:139–99.

    Google Scholar 

  78. Roberts A, Perera S, Lang B, Vincent A, Newsom-Davis J. Paraneoplastic myasthenic syndrome IgG inhibits 45Ca2+ flux in a human small cell carcinoma line. Nature. 1985;317:737–9.

    Article  CAS  PubMed  Google Scholar 

  79. Viglione MP, O’Shaughnessy TJ, Kim Y. Inhibition of calcium currents and exocytosis by Lambert-Eaton myasthenic syndrome antibodies in human lung cancer cells. J Physiol Lond. 1995;488:303–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Protti DA, Reisen R, MacKinley TA, Uchitel OD.Calcium channel blockers and transmitter release at the normal human neuromuscular junction. Neurology. 1996;46:1391–6.

    Article  CAS  PubMed  Google Scholar 

  81. Pinto A, Gillard S, Moss F, Whyte K, Brust P, Williams M, et al. Human autoantibodies specific for α1A calcium channel subunit reduce both P-type and Q-type calcium currents in cerebellar neurones. Proc Natl Acad Sci. 1998;95:8328–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Espiritu DJ, Watkins M, Dia-Monje V, Cartier GE, Cruz LJ, Olivera BM. Venomous cone snails: molecular phylogeny and the generation of toxin diversity. Toxicon. 2001;39:1899–916.

    Article  CAS  PubMed  Google Scholar 

  83. Sher E, Comola M, Nemni R, Canal N, Clementi F. Calcium channel autoantibody and non-small-cell lung cancer in patients with Lambert-Eaton syndrome. Lancet. 1990;335:413.

    Article  CAS  PubMed  Google Scholar 

  84. Motomura M, Johnston I, Lang B, Vincent A, Newsom-Davis J. An improved diagnostic assay for Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry. 1995;58:85–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Lennon VA, Kryzer TJ, Greismann GE, O’Suilleabhain PE, Windebank AJ, Woppmann A, et al. Calcium channel antibodies in the Lambert-Eaton myasthenic syndrome and other paraneoplastic syndromes. N Engl J Med. 1995;332(22):1467–74.

    Article  CAS  PubMed  Google Scholar 

  86. Motomura M, Lang B, Johnston I, Palace J, Vincent A, Newsom-Davis J. Incidence of serum anti-P/O-type and anti-N-type calcium channel autoantibodies in the Lambert-Eaton myasthenic syndrome. J Neurol Sci. 1997;147:35–42.

    Article  CAS  PubMed  Google Scholar 

  87. Bain PG, Motomura M, Newsom-Davis J, Misbah SA, Chapel HM, Lee ML, et al. Effects of intravenous immunoglobulin on muscle weakness and calcium channel antibodies in the Lambert-Eaton myasthenic syndrome. Neurology. 1996;47:678–83.

    Article  CAS  PubMed  Google Scholar 

  88. Mason WP, Graus F, Lang B, Honnorat J, Delattre JY, Valldeoriola F, et al. Paraneoplastic cerebellar degeneration and small-cell carcinoma. Brain. 1997;120:1279–300.

    Article  PubMed  Google Scholar 

  89. Trivedi R, Mundanthanan G, Amyes L, Lang B, Vincent A. Which antibodies are worth testing in subacute cerebellar ataxia? Lancet. 2000;356:565–6.

    Article  CAS  PubMed  Google Scholar 

  90. Graus F, Lang B, Pozo-Rosich P, Saiz A, Casamitjana R, Vincent A. P/Q type calcium-channel antibodies in paraneoplastic cerebellar degeneration with lung cancer. Neurology. 2002;59:764–6.

    Article  CAS  PubMed  Google Scholar 

  91. Sinha S, Newsom-Davis J, Mills K, Byrne N, Lang B, Vincent A. Autoimmune aetiology for acquired neuromyotonia (Isaacs’ syndrome). Lancet. 1991;338(8759):75–7.

    Article  CAS  PubMed  Google Scholar 

  92. Sonoda Y, Arimura K, Kurono A, Suehara M, Kameyama M, Minato S, et al. Serum of Isaacs’ syndrome suppresses potassium channels in PC-12 cell lines. Muscle Nerve. 1996;19:1439–46.

    Article  CAS  PubMed  Google Scholar 

  93. Arimura K, Watanabe O, Kitajima I, Suehara M, Minato S, Sonoda Y, et al. Antibodies to potassium channels of PC12 in serum of Isaacs’ syndrome: Western blot and immunohistochemical studies. Muscle Nerve. 1997;20:299–305.

    Article  CAS  PubMed  Google Scholar 

  94. Nagado T, Arimura K, Sonoda Y, Kurono A, Horikiri Y, Kameyama A, et al. Potassium current suppression in patients with peripheral nerve hyperexcitability. Brain. 1999;122:2057–66.

    Article  PubMed  Google Scholar 

  95. Hart IK, Waters C, Vincent A, Newland C, Beeson D, Pongs O, et al. Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia. Ann Neurol. 1997;41:238–46.

    Article  CAS  PubMed  Google Scholar 

  96. Liguori R, Vincent A, Clover L, Neudorfer C, Poggenborg J, Goßmann A, et al. Morvan’s syndrome: peripheral and central nervous system and cardiac involvement with antibodies to voltage-gated potassium channels. Brain. 2001;124:2417–26.

    Article  CAS  PubMed  Google Scholar 

  97. Buckley C, Oger J, Clover L, Tüzün E, Carpenter K, Jackson M, et al. Potassium channel antibodies in two patients with reversible limbic encephalitis. Ann Neurol. 2001;50:73–8.

    Article  CAS  PubMed  Google Scholar 

  98. Irani SR, Alexander S, Waters P, Kleopa KA, Pettingill P, Zuliani L, et al. Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia. Brain. 2010;133:2734–48.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nuffield Department of Neurological Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK

    Michelangelo Cao MD & Angela Vincent MBBS, MSc, FRCPath, FRS

Authors
  1. Michelangelo Cao MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Angela Vincent MBBS, MSc, FRCPath, FRS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Angela Vincent MBBS, MSc, FRCPath, FRS .

Editor information

Editors and Affiliations

  1. Department of Neurology, George Washington University, Washington, DC, USA

    Henry J. Kaminski

  2. Department of Pharmacology and Physiology, George Washington University, Washington, DC, USA

    Linda L. Kusner

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Cao, M., Vincent, A. (2018). Autoantibody Testing in the Diagnosis and Management of Autoimmune Disorders of Neuromuscular Transmission and Related Diseases. In: Kaminski, H., Kusner, L. (eds) Myasthenia Gravis and Related Disorders. Current Clinical Neurology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-73585-6_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-73585-6_10

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-73584-9

  • Online ISBN: 978-3-319-73585-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation