Skip to main content
SpringerLink
Log in

Autoantibody Testing of Autoimmune Neuromuscular Junction, Hyperexcitability, and Muscle Disorders

  • Chapter
  • First Online:
Neuromuscular Disorders in Clinical Practice

  • 5876 Accesses

Abstract

Serological evaluation for neuromuscular disorders expands commensurate with understanding of their autoimmune etiology. In myasthenia gravis (MG) and Lambert-Eaton syndrome (LES) and stiff person syndrome (SPS), there is a clear link between an autoantibody and disease pathogenesis, while the association of autoantibodies and inflammatory myopathies is less clear. Despite the uncertainty of the pathogenic role of autoantibodies in certain disorders, their detection may be useful in diagnosis and prognosis. This chapter reviews use of serological evaluation in diagnosis of neuromuscular junction disorders, hyperexcitability syndromes, and inflammatory muscle diseases.

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 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 449.99
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. Leite MI, Waters P, Vincent A. Diagnostic use of autoantibodies in myasthenia gravis. Autoimmunity. 2010;43:371–9.

    Article  PubMed  Google Scholar 

  2. Gilhus NE. Lambert-Eaton myasthenic syndrome; pathogenesis, diagnosis, and therapy. Autoimmune Dis. 2011;2011:973808.

    PubMed  Google Scholar 

  3. Trakas N, Zisimopoulou P, Tzartos SJ. Development of a highly sensitive diagnostic assay for muscle-specific tyrosine kinase (MuSK) autoantibodies in myasthenia gravis. J Neuroimmunol. 2011;240–241:79–86.

    Article  PubMed  Google Scholar 

  4. Guptill JT, Sanders DB. Update on muscle-specific tyrosine kinase antibody positive myasthenia gravis. Curr Opin Neurol. 2010;23:530–5.

    Article  PubMed  CAS  Google Scholar 

  5. Caress JB, Hunt CH, Batish SD. Anti-MuSK myasthenia gravis presenting with purely ocular findings. Arch Neurol. 2005;62:1002–3.

    Article  PubMed  Google Scholar 

  6. Hanisch F, Eger K, Zierz S. MuSK-antibody positive pure ocular myasthenia gravis. J Neurol. 2006;253:659–60.

    Article  PubMed  Google Scholar 

  7. Lennon V. Serologic profile of myasthenia gravis and distinction from Lambert-Eaton myasthenic syndrome. Neurology. 1997;48 Suppl 5Suppl 5:S23–7.

    Article  Google Scholar 

  8. Limburg PC, The TC, Hummel-Teppel E, Oosterhuis H. Anti-acetylcholine receptor antibodies in myasthenia gravis. I. Relation to clinical parameters in 250 patients. J Neurol Sci. 1983;58:357–70.

    Article  PubMed  CAS  Google Scholar 

  9. Howard FJ, Lennon V, Finley J, Matsumoto J, Elveback L. 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 

  10. Chan KH, Lachance DH, Harper CM, Lennon VA. Frequency of seronegativity in adult-acquired generalized myasthenia gravis. Muscle Nerve. 2007;36:651–8.

    Article  PubMed  CAS  Google Scholar 

  11. Yang L, Maxwell S, Leite MI, et al. Non-radioactive serological diagnosis of myasthenia gravis and clinical features of patients from Tianjin, China. J Neurol Sci. 2011;301:71–6.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  13. Lindstrom JM, Seybold MD, 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  PubMed  CAS  Google Scholar 

  14. Keesey JC. Clinical evaluation and management of myasthenia gravis. Muscle Nerve. 2004;29:484–505.

    Article  PubMed  Google Scholar 

  15. Sundewall AC, Lefvert AK, Olsson R. Anti-acetylcholine receptor antibodies in primary biliary cirrhosis. Acta Med Scand. 1985;217:519–25.

    Article  PubMed  CAS  Google Scholar 

  16. Pascuzzi RM, Phillips 2nd LH, Johns TR, Lennon VA. The prevalence of electrophysiological and immunological abnormalities in asymptomatic relatives of patients with myasthenia gravis. Ann N Y Acad Sci. 1987;505:407–15.

    Article  PubMed  CAS  Google Scholar 

  17. Soltys J, Gong B, Kaminski HJ, Zhou Y, Kusner LL. Extraocular muscle susceptibility to myasthenia gravis: unique immunological environment? Ann N Y Acad Sci. 2008;1132:220–4.

    Article  PubMed  CAS  Google Scholar 

  18. Kaminski H, Zhou Y, Soltys J, Kusner L. The complement hypothesis to explain preferential involvement of extraocular muscle by myasthenia gravis. In: Leigh R, Devereaux M, editors. Advances in understanding mechanisms and treatment of infantile forms of nystagmus. New York: Oxford University Press; 2008.

    Google Scholar 

  19. MacLennan C, Beeson D, Buijs A-M, Vincent A, Newsom-Davis J. Acetylcholine receptor expression in human extraocular muscles and their susceptibility to myasthenia gravis. Ann Neurol. 1997;41:423–31.

    Article  PubMed  CAS  Google Scholar 

  20. Leite MI, Strobel P, Jones M, et al. Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG. Ann Neurol. 2005;57:444–8.

    Article  PubMed  Google Scholar 

  21. Lanska DJ. Diagnosis of thymoma in myasthenics using anti-­striated muscle antibodies: predictive value and gain in diagnostic certainty. Neurology. 1991;41:520–4.

    Article  PubMed  CAS  Google Scholar 

  22. Suzuki S, Utsugisawa K, Nagane Y, Suzuki N. Three types of striational antibodies in myasthenia gravis. Autoimmune Dis. 2011;2011:740583.

    PubMed  Google Scholar 

  23. Gautel M, Lakey A, Barlow D, et al. Titin antibodies in myasthenia gravis: identification of a major immunogenic region of titin. Neurology. 1993;43:1581–5.

    Article  PubMed  CAS  Google Scholar 

  24. Mygland A, Tysnes O-B, Matre R, Volpe P, Aarli J, Gilhus N. Ryanodine receptor autoantibodies in myasthenia gravis patients with thymoma. Ann Neurol. 1992;32:589–91.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  26. Romi F, Skeie GO, Gilhus NE, Aarli JA. Striational antibodies in myasthenia gravis: reactivity and possible clinical significance. Arch Neurol. 2005;62:442–6.

    Article  PubMed  Google Scholar 

  27. Cikes N, Momoi M, Williams C, et al. Striational autoantibodies: quantitative detection by enzyme immunoassay in myasthenia gravis, thymoma and recipients of D-penicillamine and allogenic bone marrow. Mayo Clin Proc. 1988;63:474–81.

    Article  PubMed  CAS  Google Scholar 

  28. Skeie GO, Mygland Å, Aarli JA, Gilhus NE. Titin antibodies in patients with late onset myasthenia gravis: clinical correlations. Autoimmunity. 1995;20:99–104.

    Article  PubMed  CAS  Google Scholar 

  29. Mygland A, Aarli J, Matre R, Gilhus N. Ryanodine receptor antibodies related to severity of thymoma associated myasthenia gravis. J Neurol Neurosurg Psychiatry. 1994;57:843–6.

    Article  PubMed  CAS  Google Scholar 

  30. Mygland Å, Vincent A, Newsom-Davis J, et al. Autoantibodies in thymoma-associated myasthenia gravis with myositis or neuromyotonia. Arch Neurol. 2000;57:527–31.

    Article  PubMed  CAS  Google Scholar 

  31. 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  PubMed  CAS  Google Scholar 

  32. Lennon VA, Kryzer TJ, Griesmann GE, et al. Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med. 1995;332:1467–74.

    Article  PubMed  CAS  Google Scholar 

  33. 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  PubMed  CAS  Google Scholar 

  34. Lang B, Vincent A. Autoantibodies to ion channels at the neuromuscular junction. Autoimmun Rev. 2003;2:94–100.

    Article  PubMed  CAS  Google Scholar 

  35. Martin-Moutot N, De Haro L, Seagar M. Distinct evolution of calcium channel antibody types in Lambert-Eaton myasthenic syndrome. J Neuroimmunol. 2008;197:47–53.

    Article  PubMed  CAS  Google Scholar 

  36. Vernino S, Sandroni P, Singer W, Low PA. Invited article: autonomic ganglia: target and novel therapeutic tool. Neurology. 2008;70:1926–32.

    Article  PubMed  Google Scholar 

  37. Vernino S, Adamski J, Kryzer TJ, Fealey RD, Lennon VA. Neuronal nicotinic AChR antibody in subacute autonomic neuropathy and cancer-related syndromes. Neurology. 1998;50:1806–13.

    Article  PubMed  CAS  Google Scholar 

  38. Vernino S, Lennon VA. Ion channel and striational antibodies define a continuum of autoimmune neuromuscular hyperexcitability. Muscle Nerve. 2002;26:702–7.

    Article  PubMed  CAS  Google Scholar 

  39. Lennon V. Serological diagnosis of myasthenia gravis and the Lambert-Eaton myasthenic syndrome. In: Dekker M, editor. Handbook of myasthenia gravis and myasthenic syndromes. New York: Marcel Dekker; 1994. p. 149–64.

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  41. Lamb GD. Rippling muscle disease may be caused by “silent” action potentials in the tubular system of skeletal muscle fibers. Muscle Nerve. 2005;31:652–8.

    Article  PubMed  Google Scholar 

  42. Liewluck T. Immune-mediated rippling muscle disease: another inflammatory myopathy in myasthenia gravis. Arch Neurol. 2010;67:896–7.

    Article  PubMed  Google Scholar 

  43. Loukaides P, Schiza N, Pettingill P, et al. Morvan’s syndrome associated with antibodies to multiple components of the voltage-gated potassium channel complex. J Neurol Sci. 2012;312:52–6.

    Article  PubMed  Google Scholar 

  44. Newsom-Davis J, Buckley C, Clover L, et al. Autoimmune disorders of neuronal potassium channels. Ann N Y Acad Sci. 2003;998:202–10.

    Article  PubMed  CAS  Google Scholar 

  45. Shillito P, Molenaar PC, Vincent A, et al. Acquired neuromyotonia: evidence for autoantibodies directed against K+ channels of peripheral nerves. Ann Neurol. 1995;38:714–22.

    Article  PubMed  CAS  Google Scholar 

  46. Hart I, Water C, Vincent A, et al. Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia. Ann Neurol. 1997;41:238–46.

    Article  PubMed  CAS  Google Scholar 

  47. Arimura K, Sonoda Y, Watanabe O. Isaacs’ syndrome as a potassium channelopathy of the nerve. Muscle Nerve. 2002;1 Suppl 1Suppl 1:S55–8.

    Article  Google Scholar 

  48. Helfgott SM. Stiff-man syndrome: from the bedside to the bench. Arthritis Rheum. 1999;42:1312–20.

    Article  PubMed  CAS  Google Scholar 

  49. Murinson BB, Butler M, Marfurt K, Gleason S, De Camilli P, Solimena M. Markedly elevated GAD antibodies in SPS: effects of age and illness duration. Neurology. 2004;63:2146–8.

    Article  PubMed  CAS  Google Scholar 

  50. Dinkel K, Meinck HM, Jury KM, Karges W, Richter W. Inhibition of gamma-aminobutyric acid synthesis by glutamic acid decarboxylase autoantibodies in stiff-man syndrome. Ann Neurol. 1998;44:194–201.

    Article  PubMed  CAS  Google Scholar 

  51. Dalakas MC, Li M, Fujii M, Jacobowitz DM. Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies. Neurology. 2001;57:780–4.

    Article  PubMed  CAS  Google Scholar 

  52. Baekkeskov S, Aanstoot HJ, Christgau S, et al. Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature. 1990;347:151–6.

    Article  PubMed  CAS  Google Scholar 

  53. Solimena M, Folli F, Aparisi R, Pozza G, De Camilli P. Autoantibodies to GABA-ergic neurons and pancreatic beta cells in stiff-man syndrome. N Engl J Med. 1990;322:1555–60.

    Article  PubMed  CAS  Google Scholar 

  54. Murinson BB, Guarnaccia JB. Stiff-person syndrome with amphiphysin antibodies: distinctive features of a rare disease. Neurology. 2008;71:1955–8.

    Article  PubMed  CAS  Google Scholar 

  55. Panzer J, Dalmau J. Movement disorders in paraneoplastic and autoimmune disease. Curr Opin Neurol. 2011;24:346–53.

    Article  PubMed  Google Scholar 

  56. Sommer C, Weishaupt A, Brinkhoff J, et al. Paraneoplastic stiff-person syndrome: passive transfer to rats by means of IgG antibodies to amphiphysin. Lancet. 2005;365:1406–11.

    Article  PubMed  CAS  Google Scholar 

  57. Evoli A. Antibody-phenotype correlation in stiff-person syndrome. Neurology. 2008;71:1938–9.

    Article  PubMed  Google Scholar 

  58. Pittock SJ, Lucchinetti CF, Parisi JE, et al. Amphiphysin autoimmunity: paraneoplastic accompaniments. Ann Neurol. 2005;58:96–107.

    Article  PubMed  Google Scholar 

  59. Plotz P, Rider LG, Targoff IN, Raben N, Hanlon TP, Miller FW. Myositis: immunologic contributions to understanding cause, pathogenesis, and therapy. Ann Intern Med. 1995;122:715–24.

    Article  PubMed  CAS  Google Scholar 

  60. Gunawardena H, Betteridge ZE, McHugh NJ. Myositis-specific autoantibodies: their clinical and pathogenic significance in disease expression. Rheumatology. 2009;48:607–12.

    Article  PubMed  CAS  Google Scholar 

  61. Mammen AL. Autoimmune myopathies: autoantibodies, phenotypes and pathogenesis. Nat Rev Neurol. 2011;7:343–54.

    Article  PubMed  CAS  Google Scholar 

  62. Miller FW. Classification and prognosis of inflammatory muscle disease. Rheum Dis Clin North Am. 1994;20:811–26.

    PubMed  CAS  Google Scholar 

  63. Targoff IN. Autoantibodies in polymyositis. Rheum Dis Clin North Am. 1992;18:455–82.

    PubMed  CAS  Google Scholar 

  64. Hirakata M, Suwa A, Takeda Y, et al. Autoantibodies to glycyl-­transfer RNA synthetase in myositis. Association with dermatomyositis and immunologic heterogeneity. Arthritis Rheum. 1996;39:146–51.

    Article  PubMed  CAS  Google Scholar 

  65. Amato AA, Barohn RJ. Evaluation and treatment of inflammatory myopathies. J Neurol Neurosurg Psychiatry. 2009;80:1060–8.

    Article  PubMed  CAS  Google Scholar 

  66. Hirakata M. Autoantibodies to aminoacyl-tRNA synthetases. Intern Med. 2005;44:527–8.

    Article  PubMed  Google Scholar 

  67. Targoff IN. Autoantibodies and their significance in myositis. Curr Rheumatol Rep. 2008;10:333–40.

    Article  PubMed  CAS  Google Scholar 

  68. Koffman B, Rugiero M, Dalakas M. Immune-mediated conditions and antibodies associated with sporadic inclusion body myositis. Muscle Nerve. 1998;21:115–77.

    Article  PubMed  CAS  Google Scholar 

  69. Hengstman G, van Engelen B, Badrising U, van den Hoogen F, van Venrooij W. Presence of the anti-Jo-1 autoantibody excludes inclusion body myositis (letter). Ann Neurol. 1998;44:423.

    Article  PubMed  CAS  Google Scholar 

  70. Hengstman GJ, van Brenk L, Vree Egberts WT, et al. High specificity of myositis specific autoantibodies for myositis compared with other neuromuscular disorders. J Neurol. 2005;252:534–7.

    Article  PubMed  CAS  Google Scholar 

  71. Love L, Leff R, Fraser D, et al. A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. Medicine. 1991;70:360–74.

    Article  PubMed  CAS  Google Scholar 

  72. Rider LG, Miller FW. Deciphering the clinical presentations, pathogenesis, and treatment of the idiopathic inflammatory myopathies. JAMA. 2011;305:183–90.

    Article  PubMed  CAS  Google Scholar 

  73. Miller T, Al-Lozi MT, Lopate G, Pestronk A. Myopathy with antibodies to the signal recognition particle: clinical and pathological features. J Neurol Neurosurg Psychiatry. 2002;73:420–8.

    Article  PubMed  CAS  Google Scholar 

  74. Ghirardello A, Zampieri S, Iaccarino L, et al. Anti-Mi-2 antibodies. Autoimmunity. 2005;38:79–83.

    Article  PubMed  CAS  Google Scholar 

  75. Targoff IN, Reichlin M. The association between Mi-2 antibodies and dermatomyositis. Arthritis Rheum. 1985;28:796–803.

    Article  PubMed  CAS  Google Scholar 

  76. Targoff IN, Mamyrova G, Trieu EP, et al. A novel autoantibody to a 155-kd protein is associated with dermatomyositis. Arthritis Rheum. 2006;54:3682–9.

    Article  PubMed  CAS  Google Scholar 

  77. Targoff IN. Myositis specific autoantibodies. Curr Rheumatol Rep. 2006;8:196–203.

    Article  PubMed  CAS  Google Scholar 

  78. Kaji K, Fujimoto M, Hasegawa M, et al. Identification of a novel autoantibody reactive with 155 and 140 kDa nuclear proteins in patients with dermatomyositis: an association with malignancy. Rheumatology. 2007;46:25–8.

    Article  PubMed  CAS  Google Scholar 

  79. Joffe M, Love L, Leff R. Drug therapy of idiopathic inflammatory myopathies: predictors of response to prednisone, azathioprine, and methotrexate and a comparison of their efficacy. Am J Med. 1993;94:379–87.

    Article  PubMed  CAS  Google Scholar 

  80. Amato AA, Griggs RC. Treatment of idiopathic inflammatory myopathies. Curr Opin Neurol. 2003;16:569–75.

    Article  PubMed  CAS  Google Scholar 

  81. Ioannou Y, Sultan S, Isenberg D. Myositis overlap syndromes. Curr Opin Rheumatol. 1999;11:468–74.

    Article  PubMed  CAS  Google Scholar 

  82. Garton M, Isenberg D. Clinical features of lupus myositis versus idiopathic myositis: a review of 30 cases. Br J Rheumatol. 1997;36:1067–74.

    Article  PubMed  CAS  Google Scholar 

  83. Arad-Dann H, Isenberg D, Ovadia E, Shoenfeld Y, Sperling J, Sperling R. Autoantibodies against a nuclear 56 kDa protein: a marker for inflammatory muscle disease. J Autoimmun. 1989;2:877–88.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, George Washington University, 2150 Pennsylvania Ave, Washington, DC, 20037, USA

    Elham Bayat MD & Henry J. Kaminski MD

Authors
  1. Elham Bayat MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henry J. Kaminski MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elham Bayat MD .

Editor information

Editors and Affiliations

  1. School of Medicine Department of Neurology, University Hospitals Case Medical Center Case Western Reserve University, Cleveland, Ohio, USA

    Bashar Katirji

  2. Department of Neurology, George Washington University, Washington, District of Columbia, USA

    Henry J. Kaminski

  3. University School of Medicine Department of Neurology, Louis Stokes Cleveland VA Medical Center Case Western Reserve, Cleveland, Ohio, USA

    Robert L. Ruff

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Bayat, E., Kaminski, H.J. (2014). Autoantibody Testing of Autoimmune Neuromuscular Junction, Hyperexcitability, and Muscle Disorders. In: Katirji, B., Kaminski, H., Ruff, R. (eds) Neuromuscular Disorders in Clinical Practice. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6567-6_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6567-6_5

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-6566-9

  • Online ISBN: 978-1-4614-6567-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation