Diagnostic significance of measuring antibodies to cyclic type 3 muscarinic acetylcholine receptor peptides in primary Sj̈gren's syndrome

Abstract

Objective: SS is an autoimmune disease characterized by salivary and lacrimal gland dysfunction leading to dry mouth (xerostomia) and dry eyes (xerophthalmia). Anti-muscarinic acetylcholine type-3 receptor (anti-M 3R) autoantibodies have been shown to be a good serum marker in primary SS (pSS). The aim of this study was to assess the clinical correlations of anti-M 3R-derived peptide antibodies in patients with pSS. Methods: Sequences of the first to fourth cycle-M 3R (c1M 3R-c4M 3R)-derived peptide was synthesized by a solid-phase technique on an Applied Biosytems Peptide Synthesizer. Synthesized cM 3R peptide (cM 3RP) was used as substrate in an ELISA to detect IgG anti-cM 3RP antibodies in serum samples of patients and controls. The clinical and biological parameters of the diseases were also evaluated. The EULAR SS disease activity index (ESSDAI) score was used to measure disease activity in patients with primary SS. Results: (i) Anti-c2M 3RP antibodies were highly prevalent in pSS patients, and the titre is much higher than anti-c1,3,4M 3RP antibodies. (ii) The prevalence of anti-c2M 3RP antibodies in pSS, SLE, RA and healthy controls was 62.2, 7.1, 5.3 and 1.6%, respectively. The prevalence of anti-linear-2-M 3RP antibodies in pSS, SLE and RA patients and healthy controls were 56.1, 20.0, 14.7 and 9.4%. (iii) The specificity of anti-c2M 3RP antibodies was 95.1%, much higher than that of linear polypeptide (84.7%) for pSS diagnosis. (iv) In pSS patients, anti-c2M 3RP positivity had significantly increased frequency in patients who were RF or ANA positive, and had several haematological abnormalities, such as leucopenia, anaemia and thrombocytopenia. Furthermore, the ESSDAI score was significantly higher in anti-c2M 3RP-positive pSS patients (P < 0.05). Conclusion: Anti-c2M 3RP antibody was highly specific for patients with pSS. The presence of anti-c2M 3RP antibody in pSS indicates that c2M 3RP may act as an autoantigen that may play a role in the pathogenesis of pSS. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.