M3R autoantibodies mark out Sjögren’s syndrome

Japanese researchers have found what could be a new marker for Sjögren’s syndrome (SS) in autoantibodies to an antigen expressed in tear and salivary glands. In time it may be possible to determine how these are linked to the development of the disease.

The researchers looked for the autoantibodies in serum from 426 patients with one of a range of autoimmune diseases and from 128 controls to work out whether these were more prevalent in SS. These were antibodies against a synthetic peptide homologous with the second extracellular domain of the M3 muscarinic acetylcholine receptor (M3R), which has an important role in intracellular signalling.

M3R autoantibodies were significantly associated with patients who had primary (9%) or secondary (14%) SS but virtually absent in patients with rheumatoid arthritis, systemic lupus erythematosus, and the controls. Furthermore, the proportions of patients positive or negative for M3R antibodies and positive for SSA and SSB antibodies, rheumatoid factor, and antinuclear factor disclosed that the antibody was associated with patients with SSB antibody (M3R+ SSB+, 29%; M3R− SSB+, 6%). Clinical features were no different between patients with SS positive or negative for M3R autoantibodies.

The main feature of SS is infiltration of secretory glands by T lymphocytes, which react with various receptors. M3R is a candidate receptor for autoantibodies, as it is expressed in tear and salivary glands, whose function diminishes in patients with SS. Human antibodies against the second extracellular domain of M3R reduce secretion in mice and have been shown to trigger enzyme activity coupled to tear glands.