INCREASED EXPRESSION OF HUMAN THIOREDOXIN ADULT T-CELL LEUKEMIA-DERIVED FACTOR IN SJOGRENS-SYNDROME/

Objective. To determine the involvement of human thioredoxin/adult T c ell leukemia-derived factor (TRX/AD)F) in Sjogren's syndrome (SS) and the correlation with Epstein-Barr virus (EBV). Methods. Indirect immun ohistochemical techniques and reverse transcriptase polymerase chain r eaction were utilized to analyze TRX/ADF expression and the presence o f EBV, using 6 normal tissues and 23 surgical specimens. The kinetics of expression of TRX/ADF induced by EBV was examined in vitro with per ipheral blood B cells from EBV-seronegative donors. Results. Marked ex pression of TRX/ADF was found in the infiltrating B cells and the epit helial cells of salivary gland tissues from patients with SS (11 of 12 cases), but not in those from patients with other salivary gland infl ammatory conditions (0 of 11 cases) or those of normal individuals (0 of 6 cases). In immunohistologic analyses, a striking topographic corr elation between TRX/ADF and EBV was found. The coexistence of TRX/ADF messenger RNA and EBV DNA was detected by polymerase chain reaction (r = 0.75, P < 0.01). Peripheral blood B cells from EBV-seronegative don ors showed de novo synthesis of TRX/ADF following in vitro infection w ith EBV. EBV-infected B cell lines all expressed TRX/ADF. TRX/ADF was not detected in non-EBV-infected cells. Tumors in SCID mice reconstitu ted with mononuclear cells of salivary glands from SS patients, which were composed of human B cells carrying EBV DNA, were positive for TRX /ADF. Conclusion. These findings suggest that TRX/ADF expression close ly reflects the intracellular event of EBV reactivation in SS. This is also the first report to show the ectopic in vivo expression of TRX/A DF in human autoimmune disease.