Sjögrens syndrome Antimuscarinic Antibodies and Human Acinar cell Function

Introduction: Primary Sjögrens syndrome (pSS) is characterised by severe salivary gland-hypofunction (GH). For many years it has been assumed that the severe GH associated with pSS was the result of autoimmune mediated destruction of the secretory tissue within the glands. However, recent work in our laboratory has demonstrated that in many pSS sufferers there is a significant amount of functional acinar tissue remaining (Dawson et al.2001 Clin Exp Immunol 124:480-5). These findings suggest that an inhibitory, rather than destructive mechanism could be responsible for the GH. One possible inhibitory mechanism leading to GH is a functional blockade of the muscarinic type-3 receptor (M3R) on salivary acinar cells by anti-M3R autoantibodies (Bacman et al. 1996 Clin Exp Immunol 104:454-9). However, it is not known whether anti-M3R has a functional effect on intact salivary acinar tissue.

Objective: To determine whether IgG antibodies from patients with pSS can effect secretion by isolated human or mouse submandibular acinar cells.

Methods: IgG from control subjects and patients with confirmed pSS, was purified from sera by protein G affinity chromatography. The antisecretory activity of the IgG on human and mouse submandibular acinar cells was determined using a combination of fura-2 microfluorimetry and whole cell patch clamp.

Results: Chronic exposure to pSS IgG had no effect on agonist-evoked Ca2+ signals measured in either human or mouse submandibular acinar cells. Acute application of pSS IgG, but not control IgG, produced a rapidly reversible reduction in both the agonist stimulated elevation in [Ca2+]i and the conductance of the Ca2+ dependant Cl- channel in both mouse and human salivary acinar cells.

Conclusion: We demonstrate, for the first time, that the IgG fraction of pSS patients does have reversible antisecretory activity on intact salivary tissue. However, further work is needed to determine the exact mechanism of the inhibition.