Autoantibodies and Sjogren’s Syndrome: A Physiologist’s Perspective

Abstract

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.

Detection of autoantibodies against aquaporin-5 in the sera of patients with primary Sjögren’s syndrome

“…Except for the anti-parotid secretory protein and anti-M3R antibodies, most autoantibodies target antigens that are normally present inside cells. Therefore, those autoantibodies reflect the apoptotic destruction of gland tissues, that is, a result of the disease process rather than the cause of the disease [ 10 ]. The degree of salivary dysfunction in SS patients does not correlate with the degree of glandular tissue destruction [ 30 ].…”

“…The binding of autoantibodies to M3R also down-regulates the receptors from the plasma membrane by inducing internalization [ 33 ]. However, the functional data have not been reconciled with the sensitivity and specificity of the anti-M3R autoantibodies in screening trials [ 10 ]. Although anti-M3R autoantibodies have been detected in 9–100 % of SS patients depending on the method and antigens used [ 34 ], a recent meta-analysis study concluded that the anti-M3R antibody has high specificity (0.95) but relatively low sensitivity (0.43) to diagnose SS [ 35 ].…”

“…The control of salivary and lacrimal secretion is governed by muscarinic nerves through the type 3 muscarinic acetylcholine receptor (M3R). Although anti-M3R autoantibody-mediated inhibition of M3R function partially explains the dysfunction of the acinar cells [ 10 ], the pathophysiology of exocrine dysfunction observed in SS is not fully understood.…”

The Immune Factors Involved in the Pathogenesis, Diagnosis, and Treatment of Sjogren's Syndrome

“…A recent study by Passafaro et al showed that anti-M3R antibodies act as a partial muscarinic agonist, which increase prostaglandin E2 (PGE2) and cyclic AMP production through modifying Na + /K + -ATPase activity and also interfere with the secretory effect of the parasympathetic neurotransmitter [11]. Using muscle strip and whole organ functional assays, Smith and Dawson showed that IgG with anti-M3R activity from patients with SS disrupted neurotransmission in tissues throughout the mouse gastrointestinal tract [12]. Several researchers have selected the second extracellular loop as the crucial part involved in the progression of pSS since it is an epitope of anti-receptor antibodies for many G-protein coupled receptors in other autoimmune conditions.…”

Detection of Autoantibodies against Aquaporin-1 in the Sera of Patients with Primary Sjögren's Syndrome

“…Despite the focal appearance of T cells in the salivary gland, however, B cell–deficient NOD.Igµ null mice required transfer of purified IgG from patients with SS to develop the loss of secretory function, indicating the role of autoantibodies in glandular dysfunction in SS (3). Although autoantibodies to type 3 muscarinic acetylcholine receptors identified in SS can interfere with the secretory process (45), the pathophysiology of glandular dysfunction in SS has not yet been fully elucidated.…”