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Nevien Ismail-O'Keeffe, Hongen Yin, Amanda Perofsky, John A. Chiorini; Soluble BAFF-R Receptor (sBAFF-R) as a Potential treatment for Sjögren Syndrome. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1917.
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Sjögren Syndrome (SS) is a systemic autoimmune disease that is characterized by low salivary and lacrimal gland (LG) activity. One of the immunological characteristics of SS is B cells hyperactivity and serum autoantibodies. B cell-activating factor (BAFF) is a member of TNF super family, which regulates B lymphocytes proliferation and maturation, and can promote B cell survival both in vitro and in vivo. We studied the effect of neutralizing BAFF by local gene transfer of a soluble form of its receptor in non obese diabetic (NOD) mouse, which develop a Sjogren’s syndrome like phenotype and are reported to have elevated levels of BAFF expression in their salivary glands.
A recombinant Adeno-Associated virus (AAV2) was constructed encoding a soluble BAFF receptor (sBAFF-R) and expression confirmed in vitro by western and sandwich ELISA. The AAV2-BAFF-R or a control vector encoding beta galactosidase was administered to the submandibular salivary glands (SG) via retrograde cannulation of Wharton’s duct along with a reporter vector encoding luciferase at a 1:10 ratio. Successful cannulation was confirmed by xenogen imaging of the luciferase reporter vector. Salivary gland activity was measured by monitoring drinking behavior of the mice over a 2 hours interval and by measuring pilocarpine stimulated saliva production over a 20 min period at 18 weeks post vector delivery.
Statistical analysis of saliva collection and the lickometer data using student t-test, showed no statistically significant difference in salivary gland activity between the BAFF-R and the LacZ control groups suggesting BAFF-R expression had little effect on gland function compared with control mice. Immunological changes in the glands were assessed by counting the number of filtrating foci in the glands showed little decrease in lymphocytic infiltration in the BAFF-R group compared with the control group. Other immunologic changes including cytokine and immunogolobulin levels will be assessed.
Although intracelluar inhibition of BAFF has been reported to affect the Sjogren’s syndrome like phenotype in NOD mice, expression of the sBAFF-R had little effect on salivary gland activity and infiltration.
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