Antimuscarinic receptor antibodies in Sjögren's syndrome - a novel pathogenetic link between autoimmunity and glandular dysfunction?

Sjögren's syndrome (SS) is an autoimmune disease with multisystem involvement, characterised by dry eyes and mouth and various other organ manifestations. In addition to a complex network of pathological immunological processes, a dysfunction of the autonomic nervous system has also been proposed. In particular, autoantibodies reactive with the subtype-3 muscarinic acetylcholine receptor (m3AChR), a membrane protein that transmits the secretory parasympathetic neural stimuli in the salivary and lacrimal glands, have become of particular interest. It has been demonstrated that immunoglobulin G from SS patients elicits a secretory dysfunction via specific binding to the m3AChR when transferred to rodents, and to exert an inhibitory effect on the parasympathetic neurotransmission in various experimental models. We recently developed an ELISA system for the detection of antimuscarinic receptor antibodies with the use of a recombinant fusion protein containing an immunodominant epitope peptide of the receptor. With this method, we have demonstrated, a prevalence of 90% of anti-m3AChR antibodies among SS patients, an occurrence significantly higher than that in the various disease control groups. Nevertheless, many questions remain to be answered. The exact antigenic epitope within the m3AChR is a subject of debate. A validated immunoassay for clinical use is still to be developed. The precise functional role of anti-m3AChR autoantibodies in SS has not yet been determined. It would be important to demonstrate the binding of these autoantibodies in the target tissues in SS patients. If a significant clinical role of anti-m3AChR antibodies were verified, an important and potentially reversible pathogenetic step could be identified