Abstract

Systemic lupus erythematosus (SLE) is an autoimmunological disease that is characterized by an abnormal immune response and autoantibody production. We investigated the apoptotic phenomenon in freshly isolated lymphocytes from lupus patients with different disease activities and compared the apoptosis of these cells with normal healthy controls. This was based on the suggested abnormalities in lymphocyte apoptosis (murine SLE model and human lupus) and reduction of the in vitro effects. In order to determine the immunosuppressive drug effect on lymphocyte apoptosis we looked for a correlation between immunosuppressive drug doses and percentage of apoptotic lymphocytes. We analysed isolated PBMC from 32 SLE patients and 17 controls for the presence of apoptosis by means of three methods (TUNNEL, Cell cycle analysis and LISA) detecting different points of the nuclear chromatin digestion pathway. The percentage of apoptotic lymphocytes was significantly higher in patients with active SLE, compared to the inactive disease (p < 0.001) and controls (p < 0.001). In the group of patients with inactive SLE the level of apoptotic cells was slightly higher (p=0.04), in comparison with healthy individuals. We observed no correlation (p=0.15) between immunosuppressive drug doses and the percentage of apoptotic lymphocytes. We established a significant positive correlation (r=0.55, p < 0.01) between the amount of nucleosomes in the cytoplasmic fraction of cell lysates and serum antinuclear antibody levels in active lupus. These findings support the hypothesis that apoptosis being a potential source for the circulating nucleosomal DNA identified from systemic lupus erythematosus patient plasma, may contribute to autoantibody responses.

Keywords: systemic lupus erythematosus, Nucleosomes