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Rheumatology Advance Access published online on April 9, 2008
Rheumatology, doi:10.1093/rheumatology/ken064
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Functional epitope of muscarinic type 3 receptor which interacts with autoantibodies from Sjögren's syndrome patients

N.-Y. Koo1, J. Li1, S.-M. Hwang1, S.-Y. Choi1, S. J. Lee1, S.-B. Oh1, J.-S. Kim1, E. B. Lee2, Y. W. Song2 and K. Park1

1Department of Physiology, School of Dentistry and 2Internal Medicine, Seoul National University and Dental Research Institute, Seoul, South Korea.

Correspondence to: K. Park, Department of Physiology, School of Dentistry, Seoul National University, Yeongeon Dong 28, Chongno Ku, Seoul 110-749, South Korea. E-mail: kppark{at}snu.ac.kr


  Abstract

Objectives. Recently, autoantibodies directed against muscarinic type 3 receptor (M3R) have been reported in patients with primary SS. However, the precise epitope(s) of the M3R that interacts with SS autoantibodies remains unclear. The aim of this study was to identify the functional epitope of M3R which interacts with SS immunoglobulin G (IgG).

Methods. Purified IgGs were obtained from the sera of seven SS patients (six primary and one secondary SS) and two normal persons. We examined whether SS IgG inhibits M3R function and identified the epitope using six synthetic peptides covering all the extracellular domains of M3R by microspectrofluorimetry and surface plasmon resonance-based optical biosensor system (BIAcore system).

Results. A volume of 0.5 mg/ml SS IgG inhibited carbachol (CCh)-induced [Ca2+]i transient (CICT) in human submandibular gland (HSG) cells. However, co-incubation of SS IgG with the 6th peptide (514–527 amino acid region) corresponding to the third extracellular loop of M3R, recovered CICT. The result was further confirmed by BIAcore analysis. We found that the 6th peptide interacts with IgGs from three primary SS patients in a concentration-dependent manner. The synthetic peptide which consists of amino acids 228–237 corresponding to the COOH-terminus of the second extracellular loop of M3R also bound to SS IgG. However, normal IgGs did not interact with the 6th peptide.

Conclusions. The results suggest that the third extracellular loop of M3R represents a functional epitope bound by SS IgG, and thereby partly inhibits M3R function.

KEY WORDS: Autoantibodies, Muscarinic type 3 receptor, Sjögren's; syndrome, Functional epitope

Submitted 22 October 2007; revised version accepted 28 January 2008.
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