Spontaneous and induced apoptosis in systemic lupus erythematosus: Multiple assays fail to reveal consistent abnormalities

The immunologic basis of systemic lupus erythematosus (SLE) is multifactorial and still elusive. Recent advances in the held of apoptosis have suggested new paradigms for the development of lupus autoimmunity. In the present studies we examined the possibility that individual populations of T and B cells are abnormally resistant to apoptosis or that they stand out in over- or underexpressing Fas. Fas was generally overexpressed in cells freshly isolated from SLE patients but the apoptotic response to FasL was normal. We did not find increased spontaneous ongoing apoptosis in SLE lymphocytes. Normal cleavage of PARP similarly implied that the final biochemical pathway of apoptosis is relatively intact in SLE. Finally we placed special emphasis on the response of SLE patient cells to UV irradiation, especially cells from photosensitive patients, and found no difference in Fas expression. In conclusion our results indicate that SLE patients do not suffer from a major apoptotic abnormality. The results also raise questions concerning the dynamic expression of Fas and the significance of ongoing apoptosis as a risk for autoimmune disease. (C) 1999 Academic Press.