Skip to main content

Advertisement

Log in

Clinical significance of detection of antibodies to fetal and adult acetylcholine receptors in myasthenia gravis

  • Original Article
  • Published:
Neuroscience Bulletin Aims and scope Submit manuscript

Abstract

Objective

To evaluate the frequency, distribution and clinical significance of the antibodies to the fetal and/or adult acetylcholine receptor (AChR) in patients with myasthenia gravis (MG).

Methods

AChR antibodies were detected by cell-based assay in the serum of ocular MG (OMG) (n = 90) and generalized MG (GMG) patients (n = 110). The fetaltype (2α: β: Γ: δ) and adult-type (2α: β: ɛ: δ) AChR were used as antigens, and their relevance to disease presentation was assessed.

Results

The overall frequencies of anti-adult and anti-fetal AChR antibodies were similar in all 200 patients examined, with 14 having serum specific to the AChR-Γ subunit, and 22 to the AChR-ɛ subunit. The overall sensitivity when using the fetal and adult AChR antibodies was higher than that when using the fetal AChR antibody only (P = 0.015). Compared with OMG patients, the mean age at disease onset and the positive ratio of antibodies to both isoforms of the AChR were significantly higher in patients who subsequently progressed to GMG. Older patients and patients with both anti-fetal and anti-adult AChR antibodies had a greater risk for developing generalized disease [odds ratio (OR), 1.03; 95% confidence interval (CI), 1.01–1.06 and OR, 5.09; 95% CI, 2.23–11.62].

Conclusion

Using both fetal- and adult-type AChRs as the antigens may be more sensitive than using either subtype. Patients with serum specific to both isoforms are at a greater risk of progressing to GMG. Patients with disease onset at an advanced age appear to have a higher frequency of GMG conversion.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Vincent A, Palace J, Hilton-Jones D. Myasthenia gravis. Lancet 2001, 357: 2122–2128.

    Article  PubMed  CAS  Google Scholar 

  2. Yang L, Maxwell S, Leite MI, Waters P, Clover L, Fan X, et al. Non-radioactive serological diagnosis of myasthenia gravis and clinical features of patients from Tianjin, China. J Neurol Sci 2011, 301: 71–76.

    Article  PubMed  Google Scholar 

  3. Barton JJ, Fouladvand M. Ocular aspects of myasthenia gravis. Semin Neurol 2000, 20: 7–20.

    Article  PubMed  CAS  Google Scholar 

  4. Kupersmith MJ. Ocular myasthenia gravis: treatment successes and failures in patients with long-term follow-up. J Neurol 2009, 256: 1314–1320.

    Article  PubMed  Google Scholar 

  5. Kusner LL, Puwanant A, Kaminski HJ. Ocular myasthenia: diagnosis, treatment, and pathogenesis. Neurologist 2006, 12: 231–239.

    Article  PubMed  Google Scholar 

  6. Grob D. Natural history of myasthenia gravis. In: Engel AG (Ed.). Myasthenia Gravis and Myasthenic Disorders. New York, NY: Oxford University Press, 1999: 135–136.

    Google Scholar 

  7. Luchanok U, Kaminski HJ. Ocular myasthenia: diagnostic and treatment recommendations and the evidence base. Curr Opin Neurol 2008, 21: 8–15.

    Article  PubMed  Google Scholar 

  8. Na SJ, So SH, Lee KO, Choi YC. Elevated serum level of interleukin-32α in the patients with myasthenia gravis. J Neurol 2011, 258: 1865–1870.

    Article  PubMed  CAS  Google Scholar 

  9. Hong YH, Kwon SB, Kim BJ, Kim BJ, Kim SH, Kim JK, et al. Prognosis of ocular myasthenia in Korea: a retrospective multicenter analysis of 202 patients. J Neurol Sci 2008, 273: 10–14.

    Article  PubMed  Google Scholar 

  10. MacLennan C, Beeson D, Buijs AM, Vincent A, Newsom-Davis J. Acetylcholine receptor expression in human extraocular muscles and their susceptibility to myasthenia gravis. Ann Neurol 1997, 41: 423–431.

    Article  PubMed  CAS  Google Scholar 

  11. Ohta K, Fujinami A, Saida T, Nishimura M, Kuno S, Ohta M. Fre quency of anti-AChR epsilon subunit-specific antibodies in MG. Autoimmunity 2003, 36: 151–154.

    Article  PubMed  CAS  Google Scholar 

  12. Leite MI, Waters P, Vincent A. Diagnostic use of autoantibodies in myasthenia gravis. Autoimmunity 2010, 43: 371–379.

    Article  PubMed  Google Scholar 

  13. Allen JA, Scala S, Jones HR. Ocular myasthenia gravis in a senior population: diagnosis, therapy, and prognosis. Muscle Nerve 2010, 41: 379–384.

    Article  PubMed  Google Scholar 

  14. Evoli A, Tonali PA, Padua L, Monaco ML, Scuderi F, Batocchi AP, et al. Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain 2003, 126: 2304–2311.

    Article  PubMed  Google Scholar 

  15. 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: 1940–1952.

    Article  PubMed  Google Scholar 

  16. Waters P, Jarius S, Littleton E, Leite MI, Jacob S, Gray B, et al. Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Arch Neuro 2008, 65: 913–919.

    Article  Google Scholar 

  17. Kupersmith MJ, Latkany R, Homel P. Development of generalized disease at 2 years in patients with ocular myasthenia gravis. Arch Neurol 2003, 60: 243–248.

    Article  PubMed  Google Scholar 

  18. Tzartos SJ, Barkas T, Cung MT, Mamalaki A, Marraud M, Orlewski P, et al. Anatomy of the antigenic structure of a large membrane autoantigen, the muscle-type nicotinic acetylcholine receptor. Immunol Rev 1998, 163: 89–120.

    Article  PubMed  CAS  Google Scholar 

  19. Sheng JR, Li LC, Prabhakar BS, Meriggioli MN. Acetylcholine receptor-alpha subunit expression in myasthenia gravis: a role for the autoantigen in pathogenesis? Muscle Nerve 2009, 40: 279–286.

    Article  PubMed  CAS  Google Scholar 

  20. Baggi F, Annoni A, Ubiali F, Milani M, Longhi R, Scaioli W, et al. Breakdown of tolerance to a self-peptide of acetylcholine receptor alpha-subunit induces experimental myasthenia gravis in rats. J Immunol 2004, 172: 2697–2703.

    PubMed  CAS  Google Scholar 

  21. Lindstrom JM. Acetylcholine receptors and myasthenia. Muscle Nerve 2000, 23: 453–477.

    Article  PubMed  CAS  Google Scholar 

  22. Sun C, Meng F, Li Y, Jin Q, Li H, Li F. Antigen-specific immunoadsorption of anti-acetylcholine receptor antibodies from sera of patients with myasthenia gravis. Artif Cells Blood Substit Immobil Biotechnol 2010, 38: 99–102.

    Article  PubMed  CAS  Google Scholar 

  23. Kostelidou K, Trakas N, Tzartos SJ. Extracellular domains of the beta, gamma and epsilon subunits of the human acetylcholine receptor as immunoadsorbents for myasthenic autoantibodies: a combination of immunoadsorbents results in increased efficiency. J Neuroimmunol 2007, 190: 44–52.

    Article  PubMed  CAS  Google Scholar 

  24. Kaminski HJ, Kusner LL, Nash KV, Ruff RL. The gamma-subunit of the acetylcholine receptor is not expressed in the levator palpebrae superioris. Neurology 1995, 45: 516–518.

    Article  PubMed  CAS  Google Scholar 

  25. Kaminski HJ, Kusner LL, Block CH. Expression of acetylcholine receptor isoforms at extraocular muscle endplates. Invest Ophthalmol Vis Sci 1996, 37: 345–351.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Li Yang.

Additional information

These authors contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shi, QG., Wang, ZH., Ma, XW. et al. Clinical significance of detection of antibodies to fetal and adult acetylcholine receptors in myasthenia gravis. Neurosci. Bull. 28, 469–474 (2012). https://doi.org/10.1007/s12264-012-1256-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12264-012-1256-0

Keywords

Navigation