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Lupus, DNase and defective disposal of cellular debris

Apoptotic and necrotic cells are strong candidates as sources of the autoantigens that drive the autoantibody response in systemic lupus erythematosus (SLE). Defects in the physiological mechanisms for the clearance of dying cells may promote disease susceptibility to SLE. Ablation of the mouse gene Dnase1 results in the development of anti-chromatin autoimmunity and glomerulonephritis, indicating that the enzyme protects against autoimmunity by digesting extracellular chromatin.

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Figure 1: Deficiencies in molecules implicated in the disposal of effete cells promote the development of lupus:

Bob Crimi

Figure 2: A proposed model for SLE.

Bob Crimi

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Walport, M. Lupus, DNase and defective disposal of cellular debris. Nat Genet 25, 135–136 (2000). https://doi.org/10.1038/75963

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