Autoantibodies and Sjögren's syndrome: a physiologist's perspective

Sjögren's syndrome is a systemic autoimmune condition centred around salivary gland dysfunction and atrophy. There are a plethora of antibodies that mark the decline of the salivary glands, most of which relate to apoptopic mediated destruction of acinar cells. The best known of these autoantibodies, anti-Ro and anti-La form part of the diagnostic criteria for the condition. An emerging viewpoint in recent years is that glandular dysfunction precedes rather than follows glandular atrophy and attention has shifted to the interface between the immune system and the secretory process. An autoantibody against the muscarinic type 3 acetylcholine receptor occupies precisely this position because it inhibits the acetylcholine receptor which controls salivary and lacrimal fluid secretion. The consequence of identifying an autoantibody that can cause rather than simply reflect the disease process are manifold and could have a huge impact on development of therapeutic treatments. Furthermore, a "functional" autoantibody directed against an important component of the autonomic nervous system could also account for some of the extraglandular features of Sjögren's syndrome.