Role of MMP-9 in systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease characterized by a general immune response against intracellular antigens. Autoantigens (aAg) are released from apoptotic cells and assemble with autoantibodies (aAb) into immune complexes (IC). In SLE patients, aberrant cell apoptosis and defects in the clearance of dead cells and IC are observed. Although MMP-9 levels are higher in serum of SLE patients, no correlation between high MMP-9 levels and dsDNA aAb are detected. Data from the B6lpr/lprMMP-9-/- mice illustrate that MMP-9 has an important role in aAg clearance and thus that MMP-9 has a protective role in SLE. Nothing is known about the functional effects of MMP-9 on aAb or IC. I want to study the role of MMP-9 in the clearance of aAg, aAb, IC and neutrophil extracellular traps (NETs). This will be analyzed in vitro and in vivo with biochemical and biological techniques. Another unresolved issue in SLE is the implication of MMP-9 in cell death. I will check if necrotic and apoptotic cells affect different levels of MMP-9. Furthermore, the relation between the levels of MMP-9, C1q and C1q aAb will be tested. I will use a mouse model with spontaneous SLE, B6lpr/lpr mice and I will compare these mice with B6lpr/lprMMP-9-/-mice. Finally, I will analyze samples from SLE patients. The data generated in this study will be relevant for the diagnosis, for a better understanding and for the treatment of the SLE and other systemic autoimmune diseases.