Abstracts (complete list) - Wissenschaft Online

Cosima Kretz, Bartlomiej Berger, Lucie Dörner, Heiko Weyd, Ingo H. Tarner, Ulf Müller-
Ladner, Hanns-Martin Lorenz, Peter H. Krammer, Annegret Kuhn
Apoptosis in Systemic Lupus Erythematosus:
Influence on Immune Response and Peripheral Tolerance
Systemic lupus erythematosus (SLE), a human autoimmune disease, is associated with
abnormal immune responses; however, the pathogenesis of SLE is still not well
understood. It has been suggested that accumulation of apoptotic cells in the tissue and
circulation is associated with this disease. Several reports proposed that a complete and
safe disposal of apoptotic remnants might be crucial for the maintenance of peripheral
tolerance. Furthermore, it has been demonstrated that dendritic cells (DCs) cocultivated
with apoptotic cells are suppressed in their production of inflammatory
signals. The aim of this study was to investigate whether an impaired clearance of
apoptotic cells or a defect in the apoptotic pathway itself is responsible for the
manifestation of SLE. DCs derived from peripheral blood mononuclear cell samples were
analyzed regarding their functionality in clearance of apoptotic cells. Preliminary data
suggest that DCs of patients with SLE are highly sensitive to inflammatory stimuli. In
addition, we observed that the activation of patients’ DCs could still be suppressed by
apoptotic tumor cells. To determine if tolerance can be induced by apoptotic cells of SLE
patients, we co-cultivated apoptotic neutrophils with U-937, a tumor cell line displaying
DC qualities. Interestingly, we observed an increase of inflammatory parameters in
some of the patients in contrast to normal healthy donors when apoptotic neutrophils
were used. These data support our hypothesis that there is a molecular defect in
peripheral tolerance in SLE patients, which might be due to impaired apoptosis. Further
analysis is necessary to understand the mechanism and impact of these findings and to
allow therapeutic approaches in the future.