Clearance deficiency and systemic lupus erythematosus (SLE)

Area of Science:

• Immunology
• Autoimmunity
• Cell Biology

Background:

• Systemic lupus erythematosus (SLE) is a complex autoimmune disease.
• Impaired clearance of apoptotic cells may lead to autoantigen accumulation in SLE.
• Nuclear autoantigens are implicated in SLE pathogenesis.

Purpose of the Study:

• To investigate the role of impaired apoptotic cell clearance in SLE.
• To identify mechanisms leading to autoantibody production in SLE.
• To understand the development of anti-dsDNA reactivity in SLE patients.

Main Methods:

• Analysis of apoptotic cell accumulation in lymph nodes and skin of SLE patients.
• Assessing phagocytic function of granulocytes and monocytes in SLE patients.
• Evaluating macrophage migration assays using SLE patient sera.
• Analyzing DNA binding IgG autoantibodies in SLE patients.

Main Results:

• Accumulation of apoptotic cells observed in lymph node germinal centers and skin of SLE patients.
• Reduced uptake of opsonized beads by SLE patient leukocytes.
• Impaired macrophage chemoattraction by sera from a subset of SLE patients.
• High-affinity DNA-binding autoantibodies in SLE patients arise from germinal center reactions.

Conclusions:

• Impaired clearance of early apoptotic cells contributes to secondary necrosis and autoantigen exposure in SLE.
• This process favors the development of autoimmune reactions, including anti-dsDNA antibody production.
• A stepwise maturation of B cells leads to autoreactivity in SLE.