Please Sign In

Abstract

Objective: Primary Sjögren's syndrome (pSS) is characterized by autoimmune activation and the loss of function in secretory epithelia. Although extensive research has focused on changes in the patient's immune system, little is understood regarding the changes in the epithelia associated with the loss of gland function.

Methods: To identify changes in epithelial gene expression, custom microarrays were probed with cRNA isolated from minor salivary glands (MSG) of female pSS patients with low focus score and salivary flow rate and compared with gender matched healthy volunteers (HV).

Results: A significant increase in expression of the bone morphogenic protein 6 (BMP6) was observed in RNA isolated from patients compared with healthy volunteers. Over expression of BMP6 locally in the salivary gland or lacrimal glands of mice resulted in the loss of fluid secretion as well as changes in the connective tissue of the salivary gland. Assessment of the fluid movement in either isolated acinar cells of mice over expressing BMP6 or a human salivary gland cell line cultured with BMP6 identified a loss in volume regulation in these cells. Lymphocytic infiltration in the submandibular gland of BMP6 mice was increased. No significant changes were found in proinflammatory cytokines production, or auto-antibodies associated with SS, such as anti-Ro/SSA, anti-La SSB and anti-nuclear antibody (ANA) after BMP6 over expression.

Conclusion: In addition to identifying BMP6 expression in association with pSS xerostomia and xerophthalmia, this study suggests the BMP6 induced salivary and lacrimal gland dysfunction is independent from the autoantibodies and immune activation associated with pSS.