Skip to main content

Advertisement

SpringerLink
Log in

Anti-M3 muscarinic acetylcholine receptor antibodies in patients with Sjögren’s syndrome

  • Review Article
  • Published:
Modern Rheumatology

Abstract

Sjögren’s syndrome (SS) is an autoimmune disease that affects exocrine glands including salivary and lacrimal glands. Recently, autoantibodies against muscarinic acetylcholine receptor M3 (M3R) have been detected in serum from 9 to 100 % of patients with SS in addition to anti-SS-A and anti-SS-B antibodies. These observations suggest the possibility that anti-M3R antibodies could serve as a new diagnostic test in patients with SS. Some anti-M3R antibodies are directly responsible for salivary underproduction in patients with SS. Thus, strategies designed to eliminate such pathogenic antibodies could help cure SS sufferers. In this review, we summarize the current state of knowledge of anti-M3R autoantibodies in patients with SS and the correlation between B cell epitopes and the function of anti-M3R antibodies.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Dawson L, Tobin A, Smith P, Gorton T. Antimuscarinic antibodies in Sjögren’s syndrome. Arthr Rheum. 2005;52:2984–95.

    Article  CAS  Google Scholar 

  2. Li J, Ha YM, Ku NY, et al. Inhibitory effects of autoantibodies on the muscarinic receptors in Sjögren’s syndrome. Lab Invest. 2004;84:1430–8.

    Article  PubMed  CAS  Google Scholar 

  3. Scarselli M, Li B, Kim SK. Wess. Multiple residues in the second extracellular loop are critical for M3 muscarinic acetylcholine receptor activation. J Biol Chem. 2007;282:7385–96.

    Article  PubMed  CAS  Google Scholar 

  4. Naito Y, Matsumoto I, Wakamatsu E, et al. Muscarinic acetylcholine receptor autoantibodies in patients with Sjögren’s syndrome. Ann Rheum Dis. 2005;64:510–1.

    Article  PubMed  CAS  Google Scholar 

  5. Nakamura Y, Wakamatsu E, Matsumoto I, et al. High prevalence of autoantibodies to muscarinic-3 acetylcholine receptor in patients with juvenile-onset Sjögren’s syndrome. Ann Rheum Dis. 2008;67:136–7.

    Article  PubMed  CAS  Google Scholar 

  6. Koo NY, Li J, Hwang SM, et al. Functional epitopes of muscarinic type 3 receptor which interacts with autoantibodies from Sjögren’s syndrome patients. Rheumatology. 2008;47:828–33.

    Article  PubMed  CAS  Google Scholar 

  7. Tsuboi H, Matsumoto I, Wakamatsu E, Nakamura Y, Iizuka M, Hayashi T, Goto D, Ito S, Sumida T. New epitopes and function of anti-M3 muscarinic acetylcholine receptor antibodies in patients with Sjogren’s syndrome. Clin Exp Immunol. 2010;162:53–61.

    Article  PubMed  CAS  Google Scholar 

  8. Bacman SR, Berra A, Sterin-Borda L, Borda ES. Human primary Sjögren’s syndrome autoantibodies as mediators of nitric oxide release coupled to lacrimal gland muscarinic acetylcholine receptors. Curr Eye Res. 1998;17:1135–42.

    Article  PubMed  CAS  Google Scholar 

  9. Waterman SA, Gordon TP, Rischmueller M. Inhibitory effects of muscarinic receptor autoantibodies on parasympathetic neurotransmission in Sjögren’s syndrome. Arthr Rheum. 2000;43:1647–54.

    Article  CAS  Google Scholar 

  10. Gao J, Cha S, Jonsson R, Opalko J, Peck AB. Detection of anti-type 3 muscarinic acetylcholine receptor antibodies in the sera of Sjögren’s syndrome patients by use of a transfected cell line assay. Arthr Rheum. 2004;50:2615–21.

    Article  CAS  Google Scholar 

  11. Marczinovits I, Kovacs L, Gyorgy A, Toth GK, Dorgai L, Molnar J, Pokorny G. A peptide of human muscarinic acetylcholine receptor 3 is antigenic in primary Sjögren’s syndrome. J Autoimmun. 2005;24:47–54.

    Article  PubMed  CAS  Google Scholar 

  12. Kovacs L, Marczinovits I, Gyorgy A, Toth GK, Dorgai L, Pal J, Molnar J, Pokorny G. Clinical associations of autoantibodies to human muscarinic acetylcholine receptor 3213–228 in primary Sjögren’s syndrome. Rheumatology. 2005;44:1021–5.

    Article  PubMed  CAS  Google Scholar 

  13. He J, Qiang L, Ding Y, Wei P, Li YN, Hua H, Li ZG. The role of muscarinic acetylcholine receptor type 3 polypeptide (M3RP205–220) antibody in the saliva of patients with primary Sjogren’s syndrome. Clin Exp Rheumatol. 2012;30:322–6.

    PubMed  CAS  Google Scholar 

  14. Cavill D, Waterman SA, Gordon TP. Antibodies raised against the second extracellular loop of the human muscarinic M3 receptor mimic functional autoantibodies in Sjögren’s syndrome. Scand J Immunol. 2004;59:261–6.

    Article  PubMed  CAS  Google Scholar 

  15. Dawson LJ, Stanbury J, Venn N, Hasdimir B, Rogers SN, Smith PM. Antimuscarinic antibodies in primary Sjögren’s syndrome reversibly inhibit the mechanism of fluid secretion by human submandibular salivary acinar cells. Arthr Rheum. 2006;54:1165–73.

    Article  CAS  Google Scholar 

  16. Tsuboi H, Nakamura Y, Iizuka M, Matsuo N, Matsumoto I, Sumida T. Generation and functional analysis of monoclonal antibodies against the second extracellular loop of human M3 muscarinic acetylcholine receptor. Mod Rheumatol. 2012;22:264–71.

    Article  PubMed  CAS  Google Scholar 

  17. Jin M, Hwang S-M, Davies AJ, Shin Y, Bae J-S, Lee J-H, Lee EB, Song YW, Park K. Autoantibodies in primary Sjogren’s syndrome patients induce internalization of muscarinic type 3 receptors. Biochim Biophys Acta. 2012;1822:161–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. F.G. Issa for critical reading of the manuscript. This work was supported by the Research Program for Intractable Diseases, Health and Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare, Japan and the Ministry of Education, Culture, Sports, Science, and Technology.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan

    Takayuki Sumida, Hiroto Tsuboi, Mana Iizuka, Hiromitsu Asashima & Isao Matsumoto

Authors
  1. Takayuki Sumida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroto Tsuboi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mana Iizuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiromitsu Asashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Isao Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takayuki Sumida.

About this article

Cite this article

Sumida, T., Tsuboi, H., Iizuka, M. et al. Anti-M3 muscarinic acetylcholine receptor antibodies in patients with Sjögren’s syndrome. Mod Rheumatol 23, 841–845 (2013). https://doi.org/10.1007/s10165-012-0788-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10165-012-0788-5

Keywords

Search

Navigation