Objective. Sjögren's syndrome (SS) is an autoimmune condition affecting salivary glands, for which a clearly defined pathogenic autoantibody has yet to be identified. Autoantibodies that bind to the muscarinic M 3 receptors (M 3 R), which regulate fluid secretion in salivary glands, have been proposed in this context. However, there are no previous data that directly show antisecretory activity. This study was undertaken to investigate and characterize the antisecretory activity of anti-M 3 R. Methods. Microfluorimetric Ca 2؉ imaging and patch clamp electrophysiologic techniques were used to measure the secretagogue-evoked increase in [Ca 2؉] i and consequent activation of Ca 2؉ -dependent ion channels in individual mouse and human submandibular acinar cells. Together, these techniques form a sensitive bioassay that was used to determine whether IgG isolated from patients with primary SS and from control subjects has antisecretory activity.Results. IgG (2 mg/ml) from patients with primary SS reduced the carbachol-evoked increase in [Ca 2؉ ] i in both mouse and human acinar cells by ϳ50%. IgG from control subjects had no effect on the Ca 2؉ signal. Furthermore, the inhibitory action of primary SS patient IgG on the Ca 2؉ signal was acutely reversible. We repeated our observations using rabbit serum containing antibodies raised against the second extracellular loop of M 3 R and found an identical pattern of acutely reversible inhibition. Anti-M 3 R-positive serum had no effect on Ca 2؉-dependent ion channel activation evoked by the direct intracellular infusion of inositol 1,4,5-triphosphate.Conclusion. These observations show for the first time that IgG from patients with primary SS contains autoantibodies capable of damaging saliva production and contributing to xerostomia. The unusual but not unprecedented acute reversibility of the effects of anti-M 3 autoantibodies is the subject of further research.

No abstract

Glycosaminoglycan (GAG)and proteoglycans (PG)were extracted from both relatively uninflamed and severely inflamed human gingiva. The constituent GAG, Hyaluronic acid, dermatan sulphate and chondroitin 4′ sulphate, were present in the same total amount and porportions in both tissues. In contrast the PG underwent substantial breakdown in the serverly inflamed tissue as judged by anion exchange chromatography and cellulose acetate electophoresis. The findings indicate theat whereas the GAG remain apparently unchanged during inflammation, the protein moiety of the PG is catabolised leading to a loss of structural integrity.

These data represent the first demonstration of salivary acinar cell inhibition by pSS IgG; however, this inhibition was found to be reversible. Our data also show that pSS IgG binding to M3R cannot be visualized by conventional immunological approaches.

No abstract

These data suggest that increased levels of cholinesterase present in the salivary glands of patients with pSS may contribute to glandular hypofunction and provide evidence that the therapeutic enhancement of salivary secretion in patients with pSS by hydroxychloroquine may be mediated by inhibition of glandular cholinesterase activity, although further in vivo investigation is needed.

Abstract— Selected acidic glycosaminoglycans (GAG) have been used as a model series to study some binding properties of hydroxyapatite. The order of binding was heparin, heparin sulfate, dermatan sulfate/chondroitin‐4‐sulfate/chondroitin‐6‐sulfate (all similar) and hyaluronic acid, indicating that the negative charge on the molecules is a major determinant in the binding process. Both calcium and saliva pretreatrnent led to an increase in uptake of selected GAG whereas fluoride even at 1 and 3 parts/106 levels led to a graded reduction in uptake. The clinical significance of these findings may be related to the presence of certain GAG in the dental integuments and to the interaction of a chemically defined group of compounds at a specific solid surface. Such findings may also have an application in studies on endogenous mineralization. The results are in accord with the generally held view that polyanions may interact electrostatically with calcium sites present in the crystal lattice of the hydroxyapatite.

No abstract