ABNORMALITY OF OCT-1 DNA-BINDING IN T-CELLS FROM SJOGRENS-SYNDROME PATIENTS

Primary Sjogren's syndrome (SS) is an autoimmune rheumatic disease cha racterized by T cell hypoactivity. To understand the diminished T cell response to activation signals, we measured nucleoprotein DNA-binding activities regulating gene expression during T cell activation using the electrophoretic mobility shift assay. Peripheral blood lymphocytes from 9/19 SS patients were found to be defective in their ability to bind an octomer sequence (Oct-1). This Oct-1-binding phenotype remaine d stable in culture for up to 3 days prior to activation. This abnorma lity was not seen in resting T cells nor T cells from patients with sy stemic lupus erythematosus, rheumatoid arthritis (Rd), or SS accompani ed by RA. The SS Oct-1 DNA-binding abnormality correlated significantl y with an inability of cells to exit the G(0)/G(1) cell cycle phase wh en stimulated in vitro. Importantly, nucleoprotein extracts showing de creased DNA-binding activity had normal amounts of Oct-1 proteins as d etermined by immunoprecipitation, implying a functional defect in the Oct-1 protein. Moreover, defective DNA binding was corrected by treatm ent with acid phosphatase.