Increased rate of apoptosis and decreased expression of bcl-2 protein in peripheral blood lymphocytes from patients with active systemic lupus erythematosus

Abstract

Defective regulation of apoptosis may play a role in the development of autoimmune diseases, and the proto-oncogene bcl-2 is known to inhibit cells from undergoing apoptosis. We studied the rate of apoptosis and the expression of bcl-2 in peripheral blood lymphocytes of patients with systemic lupus erythematosus (SLE). A lower proportion of lymphocytes were bcl-2 + in SLE patients with active disease (median 84.9%) than in patients with inactive disease or normal (medians 95.3% and 97.1% respectively, P < 0.05). The rate of apoptosis of freshly isolated PBL was significantly higher in SLE patients than in normal (medians 1.2% vs 0.5%, p < 0.05). After 48-hour culture the apoptotic rate was further increased in SLE patients, particularly those with active disease (SLE overall 34.2%, active 62%, inactive 27.5%, normal 11.5%). These findings support the theory that in SLE patients increased apoptosis may provide a source of extracellular nuclear antigens which stimulate the autoimmune response and form immune complexes with autoantibodies.