QUANTITATIVE-ANALYSIS OF APOPTOSIS AND BCL-2 IN SJOGRENS-SYNDROME

Objective, To determine whether apoptosis plays a significant role in tissue damage of Sjogren's syndrome (SS). Methods, We performed a quan titative analysis of programmed cell death on salivary glands of 11 pa tients. Ten age matched women with sicca syndrome served as controls. Morphometric measurement of the fractional volume of acini and ducts s howing DNA strand breaks was performed in sections stained by deoxynuc leotidyl transferase assay. The extent of bcl-2 expression was determi ned in sections labeled with monoclonal antibody. The different cell p opulations infiltrating the glands were examined in tissues stained wi th anti-leukocyte common antigen and OPD4 monoclonal antibodies. Resul ts, In patients with SS, 68% of the ductal epithelium was occupied by apoptotic structures, whereas only 12% of acini showed DNA strand brea ks. Corresponding values in control salivary glands were 3 and 0.13%. bcl-2 labeling was higher in ducts than in acini of both control and p athologic glands. However, in SS a 43% (p < 0.001) and 75% (p < 0.001) reduction in bcl-2 expression was observed in ductal and acinar epith elium, respectively. In comparison with controls, the numerical densit y of CD4+ cells and plasma cells scattered throughout the interstitium was 323% and 203% higher (p < 0.001) in SS. Moreover, T helper/induce r lymphocytes represented 52% of the inflammatory foci. Conclusion, Ap optosis occurs in minor salivary glands of patients with SS with a pre vailing localization on the ductal epithelium in association with down regulation of bcl-2 and a large number of infiltrating CD4+ lymphocyte s. Thus, the destruction of glandular tissue and the loss of secretory function in SS is dependent on the activation of the suicide program of epithelial cells.