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

  • Michelangelo Cao
  • Angela Vincent
Chapter
Part of the Current Clinical Neurology book series (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.

Keywords

Myasthenia gravis Muscle-specific kinase Neuromuscular junction Voltage-gated calcium channel (VGCC) Voltage-gated potassium channel complex (VGKC-complex) Lambert-Eaton myasthenic syndrome Neuromyotonia Cell-based assays 

References

  1. 1.
    Patrick J, Lindstrom J. Autoimmune response to acetylcholine receptor. Science. 1973;180:871–2.CrossRefPubMedGoogle Scholar
  2. 2.
    Fambrough DM, Drachman DB, Satyamurti S.Neuromuscular junction in myasthenia gravis: decreased acetylcholine receptors. Science. 1973;182:293–5.CrossRefPubMedGoogle Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 5.
    Pinching AJ, Peters DK, Newsom-Davis JN.Remission of myasthenia gravis following plasma exchange. Lancet. 1976;2:1373–6.CrossRefPubMedGoogle Scholar
  6. 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.CrossRefPubMedGoogle Scholar
  7. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. 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.CrossRefPubMedGoogle Scholar
  14. 14.
    Skjei KL, Lennon VA, Kuntz NL. Muscle specific kinase autoimmune myasthenia gravis in children: a case series. Neuromuscul Disord. 2013;23:874–82.CrossRefPubMedGoogle Scholar
  15. 15.
    Evoli A. Clinical aspects of neuromuscular transmission disorders. Acta Neurol Scand Suppl. 2006;183:8–11. Review.CrossRefPubMedGoogle Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 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.CrossRefPubMedGoogle Scholar
  21. 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.CrossRefPubMedGoogle Scholar
  22. 22.
    Dau PC. Plasmpheresis therapy in myasthenia gravis. Muscle Nerve. 1980;3:468–82.CrossRefPubMedGoogle Scholar
  23. 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.CrossRefPubMedGoogle Scholar
  24. 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.CrossRefPubMedGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 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.PubMedGoogle Scholar
  27. 27.
    Maselli RA, Richman DP, Wollmann RL.Inflammation at the neuromuscular junction in myasthenia gravis. Neurology. 1991;41:1497–504.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.CrossRefPubMedGoogle Scholar
  30. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Darabid H, Perez-Gonzalez AP, Robitaille R.Neuromuscular synaptogenesis: coordinating partners with multiple functions. Nat Rev Neurosci. 2014;15:703–18. Review.CrossRefPubMedGoogle Scholar
  32. 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.CrossRefPubMedGoogle Scholar
  33. 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.CrossRefPubMedGoogle Scholar
  34. 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.CrossRefPubMedGoogle Scholar
  35. 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.CrossRefPubMedGoogle Scholar
  36. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 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.CrossRefPubMedGoogle Scholar
  39. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 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.CrossRefPubMedGoogle Scholar
  42. 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.CrossRefPubMedGoogle Scholar
  43. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Kaminski HJ. Acetylcholine receptor epitopes in ocular myasthenia. Ann N Y Acad Sci. 1998;841:309–19.CrossRefPubMedGoogle Scholar
  47. 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.CrossRefPubMedGoogle Scholar
  48. 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.CrossRefPubMedGoogle Scholar
  49. 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.CrossRefPubMedGoogle Scholar
  50. 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.CrossRefPubMedGoogle Scholar
  51. 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. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 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.CrossRefPubMedGoogle Scholar
  54. 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.CrossRefPubMedGoogle Scholar
  55. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 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.CrossRefPubMedGoogle Scholar
  58. 58.
    Romi F, Skeie GO, Aarli JA, Gilhus NE. Muscle autoantibodies in subgroups of myasthenia gravis patients. J Neurol. 2000;247:369–75.CrossRefPubMedGoogle Scholar
  59. 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.CrossRefPubMedGoogle Scholar
  60. 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.CrossRefPubMedGoogle Scholar
  61. 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.CrossRefPubMedGoogle Scholar
  62. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 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.CrossRefPubMedGoogle Scholar
  64. 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.CrossRefGoogle Scholar
  65. 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.CrossRefPubMedGoogle Scholar
  66. 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.CrossRefPubMedGoogle Scholar
  67. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 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.CrossRefPubMedGoogle Scholar
  69. 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.CrossRefPubMedGoogle Scholar
  70. 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.CrossRefPubMedGoogle Scholar
  71. 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.CrossRefPubMedGoogle Scholar
  72. 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.CrossRefGoogle Scholar
  73. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Lennon VA, Lambert EH, Whittingham S, Fairbanks V. Autoimmunity in the Lambert-Eaton myasthenic syndrome. Muscle Nerve. 1982;5:S21–5.PubMedGoogle Scholar
  75. 75.
    Newsom-Davis J, Murray NM. Plasma exchange and immunosuppressive drug treatment in the Lambert-Eaton myasthenic syndrome. Neurology. 1984;34:480–5.CrossRefPubMedGoogle Scholar
  76. 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.CrossRefGoogle Scholar
  77. 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. 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.CrossRefPubMedGoogle Scholar
  79. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 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.CrossRefPubMedGoogle Scholar
  81. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 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.CrossRefPubMedGoogle Scholar
  83. 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.CrossRefPubMedGoogle Scholar
  84. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 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.CrossRefPubMedGoogle Scholar
  86. 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.CrossRefPubMedGoogle Scholar
  87. 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.CrossRefPubMedGoogle Scholar
  88. 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.CrossRefPubMedGoogle Scholar
  89. 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.CrossRefPubMedGoogle Scholar
  90. 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.CrossRefPubMedGoogle Scholar
  91. 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.CrossRefPubMedGoogle Scholar
  92. 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.CrossRefPubMedGoogle Scholar
  93. 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.CrossRefPubMedGoogle Scholar
  94. 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.CrossRefPubMedGoogle Scholar
  95. 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.CrossRefPubMedGoogle Scholar
  96. 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.CrossRefPubMedGoogle Scholar
  97. 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.CrossRefPubMedGoogle Scholar
  98. 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.CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Nuffield Department of Neurological SciencesJohn Radcliffe Hospital, University of OxfordOxfordUK

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